Targeting the organelle for radiosensitization in cancer radiotherapy

Radiotherapy is a well-established cytotoxic therapy for local solid cancers, utilizing high-energy ionizing radiation to destroy cancer cells. However, this method has several limitations, including low radiation energy deposition, severe damage to surrounding normal cells, and high tumor resistance to radiation. Among various radiotherapy methods, boron neutron capture therapy (BNCT) has emerged as a principal approach to improve the therapeutic ratio of malignancies and reduce lethality to surrounding normal tissue, but it remains deficient in terms of insufficient boron accumulation as well as short retention time, which limits the curative effect. Recently, a series of radiosensitizers that can selectively accumulate in specific organelles of cancer cells have been developed to precisely target radiotherapy, thereby reducing side effects of normal tissue damage, overcoming radioresistance, and improving radiosensitivity. In this review, we mainly focus on the field of nanomedicine-based cancer radiotherapy and discuss the organelle-targeted radiosensitizers, specifically including nucleus, mitochondria, endoplasmic reticulum and lysosomes. Furthermore, the organelle-targeted boron carriers used in BNCT are particularly presented. Through demonstrating recent developments in organelle-targeted radiosensitization, we hope to provide insight into the design of organelle-targeted radiosensitizers for clinical cancer treatment.

Antitumor effects and radiosensitization of cytosine deaminase and thymidine kinase fusion suicide gene on colorectal carcinoma cells

AIM: To investigate the killing effect and radiosensitization of double suicide gene mediated by adenovirus on colorectal carcinoma cells. METHODS: Colorectal carcinoma cell line SW480 was transfected with adenovirus expression vector containing cytosine deaminase (CD) and thymidine kinase (TK) fusion gene. The expression of CD-TK fusion gene was detected by reverse transcriptase-polymerase chain reaction. The toxic effect of ganciclovir (GCV) and 5-fluorocytosine (5-FC) on infected cells was determined by MTT assay. The radiosensitization of double suicide gene was evaluated by clonogenic assay. RESULTS: After prodrugs were used, the survival rate of colorectal carcinoma cells was markedly decreased. When GCV and 5-FC were used in combination, the cytotoxicity and bystander effect were markedly superior to a single prodrug (X2 = 30.371, P<0.01). Both GCV and 5-FC could sensitize colorectal carcinoma cells to the toxic effect of radiation, and greater radiosensitization was achieved when both prodrug were used in combination. CONCLUSION: CD-TK double suicide gene can kill and radiosensitize colorectal carcinoma cells.

Comparative study of the chitooligosaccharides effect on the proliferation inhibition and radiosensitization of three types of human gastric cancer cell line

Objective:To observe the chitooligosaccharides(COS) effect on the proliferation inhibition and radiosensitivity of three types of human gastric cancer cell line.Mothods:CCK-8 assay was employed to obtain the inhibition ratio of COS on BGC823 cells,MKN45 cells and SGC7901 cells at 48 h after treatment and the proliferation-inhibition curve was drawn with the inhibition ratio of COS on three types of cells.The clonogenic assay was used to detect the cell viability of 0,1,2,4,6 and 8 Gy(6 dose grades) in RAY group and RAY+COS group after X-ray,and the cell survival curve was used to analyze the sensitization enhancement ratio of COS.Flow cytometry was employed to detect cell cycle and apoptosis rate in control group,RAY group and RAY+COS group after 48 h treatment.Results:COS inhibited the proliferation of three types of cells.The inhibition rate was positively correlated with the concentration of COS,and the susceptibility of MKN45 cells,SGC7901 cells and BGC823 cells to COS decreased in turn.The cell viability decreased gradually with the increasing radiation dose in RAY group and RAY+COS group(P<0.01).The cell viabilities of RAY+COS group were lower than those of RAY group at all the dose grades under X-ray exposure(P<0.01),and the sensitization enhancement ratios of COS on BGC823 cells,MKN45 cells and SGC7901 cells were 1.06,1.28 and 1.15 respectively.In controlled trials,apoptosis rate and percentage in the G_2/M phase of three types of cells in RAY+COS group were higher than those in control group and RAY group,and percentage in the S phase and the G_0/G_1 phase in RAY+COS group were lower than those in the other two groups(P<0.01).Conclusions:COS can inhibit the proliferation of three types of human gastric cancer cells and enhance the radiosensitivity by inducing apoptosis and G_2/M phase arrest.

Anti-proliferation and radiosensitization effects of chitooligosaccharides on human lung cancer line Hep G2

Objective: To observe the anti-proliferation and radiosensitization effect of chitooligosaccharides(COS) on human lung cancer cell line Hep G2. Methods: CCK-8 assay was employed to obtain the inhibition ratio of COS on Hep G2 cells at 24 h after treatment. The clonogenic assay was used to analyze the cell viability of RAY group and RAY+COS group with X-ray of 0, 1, 2, 4, 6 and 8 Gy, and the cell survival curve was used to analyze the sensitization ratio of COS. Flow cytometry was employed to detect cell cycle and apoptosis rate in control group, RAY group and RAY+COS group after 24 h treatment. Results: COS inhibited the proliferation of Hep G2 cells, and the inhibition rate positively correlated with the concentration of COS. The cell viability decreased with increasing exposure dose in RAY group and RAY+COS group. The cell viabilities of RAY+COS group were lower than those of RAY group at the dose of 4, 6 and 8 Gy(P<0.05), and the sensitization ratio of COS was 1.19. There were higher percentage at G2/M phase and apoptosis rate, and lower percentage at S phase in RAY+COS group versus the other two groups(P<0.01). Conclusions: COS can inhibit the proliferation of Hep G2 cells, and enhance the radiosensitization of Hep G2 cells, induce apoptosis and G2/M phase arrest.

Inhibiting PI3K/Akt Pathway Increases DNA Damage of Cervical Carcinoma HeLa Cells by Drug Radiosensitization

This study examined the role of PI3K/Akt pathway in radiosensitization of DNA damage of cervical carcinoma cells.The 50% inhibition concentration(IC50) of cisplatin and docetaxel in HeLa cells was detected by Mono-nuclear cell direct cytotoxicity assay(MTT) in vitro.HeLa cells were treated by cisplatin/docetaxel of 10 percent of IC20 alone or combined with LY294002 for 24 h,and then radiated by different doses of X-ray.The cell survival ratio was obtained by means of clone formation.One-hit multi-target model was fitted to the cell survival curve to calculate dose quasithreshold(Dq),mean lethal dose(D0),2Gy survival fraction(SF2) and sensitization enhancement ratio(SER).The pAkt and total Akt expression was detected by Western blotting and DNA damage by neutro-comet electrophoresis.The HeLa cells were randomly divided into 7 groups in terms of different treatments:Control;radiation treatment(RT) group;LY294002+RT group;cisplatin+RT group;docetaxel+RT group;LY294002+cisplatin+RT group;LY294002+docetaxel+RT group.The apoptosis ratio of each group was measured by flow cytometry.The results showed that docetaxel and cisplatin significantly enhanced the phosphorylation of Akt in radiation-treated HeLa cells.The Dq,D0 and SF2 in LY294002-contained groups were lower than those in docetaxel or cisplatin+RT group.The SER in the LY294002+docetaxel+RT group was 1.35 times that of the docetaxel+RT group,and that in the LY294002+cisplatin+RT group 1.26 times that of the cisplatin+RT group.The Comet electrophoresis showed that tail distance in the LY294002+cisplatin+RT group or LY294002+docetaxel+RT group was longer than in the cisplatin+RT group or docetaxel+RT group.The apoptosis ratio in the LY294002+cisplatin+RT group or LY294002+docetaxel +RT group was higher than in the cisplatin+RT group or docetaxel+RT group.It was concluded that inhibiting PI3K/Akt pathway can increase the effect of docetaxel and cisplatin on the radiosensitivity of HeLa cells and DNA damage resulted from radiation.

Docetaxel shows radiosensitization in human hepatocellular carcinoma cells

AIM: To determine the radiosensitizing potential of docetaxel in human hepatocellular carcinoma SMMC-7721 cells and its mechanisms.METHODS: SMMC-7721 cells were incubated with docetaxel at 0.125, 0.25, and 0.5 nmoL/L for 24 h and at 0.125 and 0.25 nmol/L for 48 h before irradiation. Radiation doses were given from 0 to 10 Gy. Cell survival was measured by a standard clonogenic assay after a 9-d incubation. The reactive oxygen species (ROS) and glutathione (GSH) are detected after being given the same dose of docetaxel for the same time. RESULTS: The sensitization enhancement ratios (SER) for SMMC-7721 cells determined at the 50% survival level were 1.15, 1.21 and 1.49 at 0.125, 0.25, and 0.5 nmol/L for pre-incubation of 24 h, respectively; the SER were 1.42, 1.67 at 0.125 and 0.25 nmol/L, for pre-incubation of 48 h, respectively. The ROS of SMMC-7721 cells increased and GSH decreased after pretreatment with the same doses of docetaxel for 24 or 48 h.CONCLUSION: A radiosensitizing effect of docetaxel could be demonstrated unambiguously in this cell line used. In addition, our data showed that the mechanism of radiopotentiation by docetaxel probably does not involve a G2/M block in SMMC-7721 cells, and ROS generation and GSH deletion may play a key role in the radiosensitizing effect of docetaxel.

Effect and mechanism of CyPA in radiosensitization of lung adenocarcinoma using CRISPR/Cas9 technology

Objective:To explore the role of cyclophilin A(CyPA)in sensitization of lung adenocarcinoma to radiotherapy using CRISPR/Cas9 technology.Methods:A CyPA knockout human lung adenocarcinoma cell line H1975 was established by CRISPR/Cas9 technology.Groups included a control group(wildtype),CyPA knockout group,traditional Chinese medicine(TCM)extract with Fuzhengzengxiao decoction group,and TCM extract with Fuzhengzengxiao decoction t CyPA knockout group.Each group was exposed to radiation at doses of 0,2,4,6,and 8 Gy.After 24 h,MTT assays were used to determine the survival rate of lung cancer cells and calculate radiosensitivity.The qPCR was used to measure mRNA expression of DDIT3,CDKN1A,and CDC25A associated with DNA damage repair.Results:Without irradiation,Fuzhengzengxiao decoction reduced the survival rate of lung adenocarcinoma cells(P<.0001).After irradiation,TCM extract with Fuzhengzengxiao decoction,CyPA knockout,and TCM extract with Fuzhengzengxiao decoction t CyPA knockout groups had reduced survival rates(P<.0001)and radiosensitivity was increased significantly.Expression of DDIT3,CDKN1A,and CDC25A was upregulated after knockout of CyPA(P<.0001).Expression of DDIT3 and CDC25A was increased after irradiation in wildtype cells treated with TCM extract with Fuzhengzengxiao decoction(DDIT3,P<.0001;CDC25A,P紏.0059).The TCM extract with Fuzhengzengxiao decoction t CyPA knockout group also had increased expression of DDIT3 and CDC25A after irradiation(P<.0001).Conclusion:Fuzhengzengxiao decoction significantly decreases the survival rate of lung cancer cells,and its mechanism may be related to radiosensitization by decreasing expression of CyPA and inducing G1/S cell cycle arrest.

Investigation of the radiosensitization effect in FePt nanopaticle clusters with Monte Carlo simulation

Nanoparticles(NPs) with high-Z atoms have been widely studied as radiosensitizers for use in cancer therapy. Over the past few years, the application of FePt NPs has attracted extensive research interest. Promising results have been obtained, yet limited knowledge is available regarding its potential use as a radiosensitizer.The goal of this study is to investigate the radiosensitization capability of FePt nanoparticle clusters(NPCs) under the exposure of kilovoltage photons using Monte Carlo simulation. First, in order to obtain a realistic distribution of NPCs on the microscopic level, Hela cells were incubated with FePt NPs, and the distribution of NPCs was obtained by optical microscope images and X-ray NanoCT experiments. Based on these images, a simplified cellmodel was developed to evaluate the DER of two material types(FePt and FePt_3). For each type, the dependence of DER on the thickness and angular distribution of NPCs on the surface of the cell membrane was studied quantitatively. Our results suggest that DER is strongly dependent on photon energy and the distance from the NPCs to the nucleus. Fe_1 Pt_3 is able to achieve a higher DER relative to Fe_1 Pt_1. For a given X-ray energy, DER demonstrates an initial increase to a maximum value but gradually saturates as the thickness of NPCs increases from 250 up to 2000 nm due to a trapping effect. The impact on DER resulting from the coexistence of the NPCs on the cell membrane and the nuclear membrane was also investigated.

Radiosensitization by microRNA30a-5p in a nude mouse model with subcutaneous lung-cancer xenograft

Objective We aimed to observe the radiosensitization effect of mir-30a-5p in a nude mouse model with subcutaneous lung-cancer xenograft and to explore the underlying mechanism.Methods A549 cell lines with either stable upregulation or downregulation of mir-30a-5p,and their negative control,were transfected with lentivirus vectors.These cell lines were used to establish a nude mouse model with subcutaneous lung-cancer xenograft.Each group was randomly divided into irradiated and non-irradiated groups.The radiosensitization effect of mir-30a-5p in vivo was studied by observing xenograft growth trends and tumor weight.The mechanisms involved in this radiosensitization were investigated by detecting expressed radiosensitization-related proteins,using immunohistochemistry and Western blotting.Results The expression level of mir-30a-5p in the lenti-mir-30a-5p group was higher than that in the negative control(lenti-GFP)group and lower in the lenti-inhibitor group(P<0.05).Subcutaneous lung-cancer xenografts in the irradiation group and lenti-mir-30a-5p increased in size slowly;tumors were lighter and tumor inhibition rates were higher than those in the non-irradiation and lenti-GFP groups.In contrast,the opposite of these effects was observed in the lenti-inhibitor group.Immunohistochemistry and Western blotting indicated that ATM protein expression level was lower in the lenti-mir-30a-5p group,with or without irradiation,compared to that in the lenti-GFP group.ATM protein levels were higher in the lenti-inhibitor groups.The phosphorylation level of ATM at residue 1981 was low in the groups without irradiation and increased significantly after irradiation(P<0.05).Moreover,the phosphorylation level was lower in the lenti-mir-30a-5p group and higher in the lenti-inhibitor group than that in the lenti-GFP group after irradiation(P<0.05).Conclusion Mir-30a-5p enhanced the radiosensitivity of nude mice with subcutaneous lung-cancer xenografts by inhibiting ATM phosphorylation.

3-59 Radiosensitization to X-ray Radiation by Telomerase Inhibitor MST-312 in Human Hepatoma HepG2 cells

Telomerase inhibitor MST-312 is a new compound derived from epigallocatechin gallate (EGCG)[1]. Our resultsdemonstrated that 4 M MST-312 not only showed lower cytotoxicity, but also inhibited telomerase activity inHepG2 cells. Therefore, in our experiments, 4 M MST-312 was chosen to study radiosensitization and relatedmechanisms. -H2AX foci are considered as an indicator of DNA damages[2]. The immunofluorescence stainingresults showed the number of -H2AX foci in the pretreatment with MST-312 followed by 2 Gy X-ray irradiationgroup. However, as shown in Fig. 1, the formation of Rad51 foci in the combined treatment group was blockedoutside the nuclear of HepG2 cells, when compared with the irradiation alone group. JC-1 staining showed thatMST-312 pretreatment, followed by X-ray irradiation, caused increase of the green/red fluorescence intensity ratio(ΔΨm) compared with X-ray irradiation alone. Meanwhile, MST-312 pretreatment followed by X-ray irradiationelevated expression of p53 protein and decreased expression of caspase-3 as well as fraction of Bcl-2 / Bax.

Surface-ligand effect on radiosensitization of ultrasmall luminescent gold nanoparticles

Gold nanoparticles(AuNPs)could serve as pot ential radiother apy sensitizers because of their exceptional biocompatibility and high.Z material nature;however,since in vitro and in vivo behaviors of AuNPs are determined not only by their particle size but also by their surface chemistries,whether surface ligands can affect their radiosensitization has seldom been investi-gated in the radiosensitization of AuNPs.By conducting head-to-head comparison on radio-sensitization of two kinds of ultrasmall(~2 nm)near-infrared(NIR)emitting AuNPs that are coated with zwitterionic glutathione and neutr al polyethylene glyol(PEG)ligands,respectively,we found that zwitterionic glut athione coated AuNPs(GS-AuNPs)can reduce survival rates of MCF-7 cells under irr adiation of clinically used megavoltage photon beam at low dosage of~2.25 Gy.On the other hand,PEG-AuNPs can serve as a radiation-protecting agent and enabled MCF-7 cells more resistant to the irradiation,clearly indicating the key role of surface cheistry in radiosensitization of AuNPs.More detailed studies suggested that such difference was inde-pendent of cellular uptake and its eficiency,but might be related to the ligand-induced difference in photoelectron generation and/or inter actions between AuNPs and X-ray triggered reactive oxygen species(ROS).

ANTP-SMACN7 fusion peptide alone induced high linear energy transfer irradiation radiosensitization in non-small cell lung cancer cell lines

Objective:The aim of the present study was to investigate the mechanisms responsible for the radiation-sensitizing effect of antennapedia proteins,ANTP-SMACN7,on lung cancer cells treated with accelerated carbon and Fe particle irradiation.Methods:The ANTP-SMACN7 fusion peptide was synthesized and linked to fluorescein isothiocyanate to determine its ability to penetrate cells.A549 and NCI-H460 cells,human non-small cell lung cancer(NSCLC)cell lines,were irradiated with X-ray or high linear energy transfer(LET)irradiation with or without ANTP-SMACN7 treatment.Cellular survival,apoptosis,and protein expression were studied by colony formation assays,flow cytometry,and western blot analyses,respectively.Results:ANTP-SMACN7 fusion proteins entered the cells and promoted A549 and NCI-H460 cell high LET irradiation radiosensitization.High LET irradiation was more efficient for clonogenic cell killing and the induction of apoptosis(P<0.05).Treatment with ANTP-SMACN7 significantly reduced the A549 and NCI-H460 cell clone-forming percentages and increased apoptosis through inhibition of the X-linked inhibitor of apoptosis protein and the activation of caspase-3 and caspase-9.Conclusions:Regarding pharmaceutical radiosensitization,these findings provided a way to improve high-LET clinical radiotherapy for NSCLC patients.

Radiosensitization of human pancreatic cancer by piperlongumine analogues

Radiotherapy is commonly used to treat advanced pancreatic cancers and can improve survival by2 months in combination with gemcitabine.However,prognosis and survival improvement remain unsatisfactory,and effective therapies are urgently needed.Piperlongumine has been demonstrated to have therapeutic potentials against various cancers.In this study,we synthesized a series of piperlongumine derivatives and provided evidence that piperlongumine derivatives could be used as effective radiosensitizers in pancreatic cancer.Two compounds enhanced the radiosensitivity of Panc-1 and SW1990 cells.In a pancreatic bi-flank xenograft tumor model,they significantly inhibited tumor growth.Piperlongumine derivatives could induce reactive oxygen species(ROS)expression and regulate the Keapl-Nrf2 protective pathway with enhancement of radiation-induced DNA damage,G2/M-phase cell cycle arrest,and apoptosis.Collectively,our data offer a proof of concept for the use of piperlongumine derivatives as a novel class of radiosensitizers for the treatment of pancreatic cancer.

TOPK Inhibition Enhances the Sensitivity of Colorectal Cancer Cells to Radiotherapy by Reducing the DNA Damage Response

Objective Abnormal expression of T-lymphokine-activated killer cell-originated protein kinase(TOPK)was reported to be closely related to the resistance of prostate cancer to radiotherapy and to targeted drug resistance in lung cancer.However,the role of TOPK inhibition in enhancing radiosensitivity of colorectal cancer(CRC)cells is unclear.This study aimed to evaluate the radiosensitization of TOPK knockdown in CRC cells.Methods The expression of TOPK was detected in CRC tissues by immunohistochemistry,and the effect of TOPK knockdown was detected in CRC cells by Western blotting.CCK-8 and clonogenic assays were used to detect the growth and clonogenic ability of CRC cells after TOPK knockdown combined with radiotherapy in CRC cells.Furthermore,proteomic analysis showed that the phosphorylation of TOPK downstream proteins changed after radiotherapy.DNA damage was detected by the comet assay.Changes in the DNA damage response signaling pathway were analyzed by Western blotting,and apoptosis was detected by flow cytometry.Results The expression of TOPK was significantly greater in CRC tissues at grades 2–4 than in those at grade 1.After irradiation,CRC cells with genetically silenced TOPK had shorter comet tails and reduced expression levels of DNA damage response-associated proteins,including phospho-cyclin-dependent kinase 1(p-CDK1),phospho-ataxia telangiectasia-mutated(p-ATM),poly ADP-ribose polymerase(PARP),and meiotic recombination 11 homolog 1(MRE11).Conclusions TOPK was overexpressed in patients with moderately to poorly differentiated CRC.Moreover,TOPK knockdown significantly enhanced the radiosensitivity of CRC cells by reducing the DNA damage response.

Enhancing the radiosensitivity of colorectal cancer cells by reducing spermine synthase through promoting autophagy and DNA damage

BACKGROUND Colorectal cancer(CRC),the third most common cancer worldwide,has increasingly detrimental effects on human health.Radiotherapy resistance diminishes treatment efficacy.Studies suggest that spermine synthase(SMS)may serve as a potential target to enhance the radiosensitivity.AIM To investigate the association between SMS and radiosensitivity in CRC cells,along with a detailed elucidation of the underlying mechanisms.METHODS Western blot was adopted to assess SMS expression in normal colonic epithelial cells and CRC cell lines.HCT116 cells were transfected with control/SMS-specific shRNA or control/pcDNA3.1-SMS plasmids.Assessments included cell viability,colony formation,and apoptosis via MTT assays,colony formation assays,and flow cytometry.Radiosensitivity was studied in SMS-specific shRNA-transfected HCT116 cells post-4 Gy radiation,evaluating cell viability,colony formation,apoptosis,DNA damage(comet assays),autophagy(immunofluorescence),and mammalian target of rapamycin(mTOR)pathway protein expression(western blot).RESULTS Significant up-regulation of SMS expression levels was observed in the CRC cell lines.Upon down-regulation of SMS expression,cellular viability and colonyforming ability were markedly suppressed,concomitant with a notable increase in apoptotic indices.Furthermore,attenuation of SMS expression significantly augmented the sensitivity of HCT116 cells to radiation therapy,evidenced by a pronounced elevation in levels of cellular DNA damage and autophagy.Impor tantly,down-regulation of SMS corresponded with a marked reduction in the expression levels of proteins associated with the mTOR signaling pathway.CONCLUSION Knocking down SMS attenuates the mTOR signaling pathway,thereby promoting cellular autophagy and DNA damage to enhance the radiosensitivity of CRC cells.

MiR-450b-5p enhances the radiosensitivity of HR^(+) and HER2^(−) breast cancer by targeting CDK6

Background:The sensitivity of breast cancer cells to radiation is a key cause of locoregional recurrence after postoperative radiotherapy.Several studies have reported that microRNAs(miRNAs)are involved in the radiosensitivity of human breast cancer cells.One miRNA microarray study showed that miR-450b-5p was overexpressed 13.3-fold in patients with estrogen receptor–positive(ER^(+))and human epidermal growth factor receptor 2–negative(HER2−)breast cancer and no local relapse compared with local relapse patients.However,its underlying mechanism of action remains unknown.Methods:The predicted target mRNAs of miR-450b-5p were screened using the TargetScan,miRDB,and miRWalk databases.Western blotting,quantitative polymerase chain reaction,and dual-luciferase reporter assays explored the association between cyclindependent kinase 6(CDK6)and miR-450b-5p.The cell counting kit-8 assay and flow cytometry detected the proliferation of transfected MCF7 cells.Colony formation and xenograft tumors detected the radiosensitivity of the transfected MCF7 cells.Results:Bioinformatics analysis,Western blotting,quantitative polymerase chain reaction,and dual-luciferase reporter assays demonstrated that CDK6 was the target gene of miR-450b-5p.Furthermore,in vitro and in vivo experiments showed that miR-450b-5p inhibited MCF7 cell proliferation and cell cycle progression,increased the sensitizer enhancement ratio,and decreased the volume of xenograft tumors after irradiation by regulating CDK6.Conclusions:This study demonstrates that miR-450b-5p enhances the radiosensitivity of hormone receptor–positive(HR^(+))and HER2−breast cancer cells and elucidates its mechanism.miR-450b-5p may be considered a therapeutic target in HR^(+)and HER2−breast cancer treated with radiotherapy.

Radiosensitization mechanism of riboflavin in vitro

Riboflavin, suggested to be a radiosensitizer, was studied in murine thymocytes and human hepatoma L02 cell line in vitro with MTT method and fluorescence microscopy. When the murine thymocytes treated with 5-400 μmol/L riboflavin were irradiated by 5 Gy 60Co γ ionizing radiation, the low concentration groups, i.e. treated with 5-50 μmol/L riboflavin, showed a different surviving fractions-time relating correlation compared with the high concentration groups, i.e. treated with 100-400 μmol/L riboflavin. The former had a high survival level at the end of irradiation, but which, after 4-h incubation, decreased rapidly to a low level. On the contrary, the high concentration groups showed a low survival level at the end of irradiation, and a poor correlation was found between the surviving fraction and the incubation time, after 4 h a little difference was observed. The results of fluorescence microscopy indicated that under low concentration conditions, the riboflavin localized mainly in nucleus (both perinuclear area and inside of nuclear membrane), while under high concentration conditions, intensive riboflavin also localized around cytoplasmic membranes. Thus we can conclude: the riboflavin had radiosensitivity effect on DNA under low concentration conditions, and enhanced the damage to cytoplasmic membrane under high concentration conditions. Also the most effective concentration of riboflavin can be evaluated to be approximate 100 μmol/L.

Advancements in understanding mechanisms of hepatocellular carcinoma radiosensitivity:A comprehensive review

Primary liver cancer is a significant health problem worldwide.Hepatocellular carcinoma(HCC)is the main pathological type of primary liver cancer,accounting for 75%-85%of cases.In recent years,radiotherapy has become an emerging treatment for HCC and is effective for various stages of HCC.However,radiosensitivity of liver cancer cells has a significant effect on the efficacy of radiotherapy and is regulated by various factors.How to increase radiosensitivity and improve the therapeutic effects of radiotherapy require further exploration.This review summarizes the recent research progress on the mechanisms affecting sensitivity to radiotherapy,including epigenetics,transportation and metabolism,regulated cell death pathways,the microenvironment,and redox status,as well as the effect of nanoparticles on the radiosensitivity of liver cancer.It is expected to provide more effective strategies and methods for clinical treatment of liver cancer by radiotherapy.

Biomarkers for enhancing the radiosensitivity of nasopharyngeal carcinoma

Nasopharyngeal carcinoma(NPC) is a common head and neck malignancy. The incidence of NPC is higher in Southern China and Southeast Asia compared with Western countries. Given its high radiosensitivity, the standard treatment for NPC is radiotherapy. However, radioresistance remains a serious obstacle to successful treatment. Radioresistance can cause local recurrence and distant metastases in some patients after treatment by radiation. Thus, special emphasis has been given to the discovery of effective radiosensitizers. This review aims to discuss the biomarkers, classified according to the main mechanisms of radiosensitization, which can enhance the sensitivity of NPC cells to ionizing radiation.