Mechanism of Anti-tumor Effects of Viola Medicinal Materials Based on Network Pharmacology and Molecular Docking

[Objectives]To explore the relationship between anti-tumor components,targets,and pathways involved in Viola medicinal materials,study its main active components,and evaluate its inhibitory activity.[Methods]Through network pharmacological analysis,molecular docking simulation experiments and in vitro experiments,the main components and corresponding targets of Viola were screened out,and their anti-tumor signaling pathways were confirmed.MTT colorimetric assay was used to investigate the inhibitory effect of different extraction layers of Viola on the growth of tumor cells.[Results]18 anti-tumor active components such as 2α,19α-Dihydroxyursolic acid,Corlumine,Madolin U,Trifolirhizin and etc.,and 52 action targets such as PTGS2,PTGS1,P2RX7,MMP1,and GABRB3,and anti-tumor signaling pathways were confirmed.The results of molecular docking showed that all the selected Viola compounds had good binding activity.The results of MTT colorimetric assay showed that the petroleum ether layer and n-butanol layer had a good inhibitory effect on the growth of tumor cell lines.[Conclusions]Viola medicinal materials have the potential of anti-tumor,triterpenoids and flavonoids may be the main active components,and the petroleum ether layer and n-butanol layer have better inhibitory effect on the growth of tumor cells.

Advances in Research of Anti-tumor Effect of Aconiti Radix

In this paper,the anti-tumor effects of Aconiti Radix were reviewed and summarized,and the clinical feasibility of Aconiti Radix as a potential anti-tumor drug was analyzed,in order to provide a useful reference for the future research and development of new anti-cancer drugs of Aconiti Radix.

Research progress on the anti-tumor effect of Codonopsis pilosula

Currently,the mortality rate of malignant tumors ranks second globally,surpassed only by cardiovascular and cerebrovascular diseases.The treatment of malignant tumors poses a formidable challenge to both modern medicine and traditional Chinese medicine(TCM).To date,TCM has developed a substantial foundational theoretical understanding and accumulated significant clinical experience in combating tumors.According to TCM foundational theories,"Qi deficiency"is a critical symptom associated with cancer,and"fortifying the body's vitality while expelling pathogens"is the cornerstone of TCM's approach to tumor treatment and bodily balance.Codonopsis pilosula(CP),a Qi-invigorating herb,is known to invigorat the spleen,benefit the lungs,nourish the blood,and promote bodily fluids.It is often employed as a substitute for ginseng in clinical settings.Prolonged clinical observations have identified key active constituents of CP,such as Codonopsis polysaccharides,isoimperatorin,saponins,lobetyolin,sesquiterpene lactones,and muscone.These ingredients exhibit various therapeutic properties,including anti-tumor,immunomodulatory,anti-infective,antioxidant,and hematopoiesis-enhancing effects.Additionally,when CP is combined with other TCM herbs like Astragalus and Atractylodes macrocephala,it bolsters the body's vital energy and rejuvenates both Qi and blood.CP can be used in combination with chemotherapy agents to mitigate the adverse effects of radiotherapy and chemotherapy.Moreover,CP demonstrates potential in preventing precancerous lesions.This review summarizes recent research findings on the anti-tumor properties of CP,elucidates the anti-tumor effects and molecular mechanisms of its active components,provides a basis for promoting the utilization of CP resources and its active constituents,and offers insights for the research and development of new anti-tumor drugs.

Anti-tumor Effect and Protective Effect on Chemotherapeutic Damage of Water Soluble Extracts from Hedyotis diffusa

Bai-Hua-She-She-Cao Hedyotis diffusa Willd. (Ru-biaceae) is a medicinal herbwidely distributed in northeast Asian countries. In traditional Chinese medicine, it has the effectof 'clearing away heat and toxic material, promoting blood circulation and removing blood stasis'.It is a well known Chinese folk-medicine used for the treatment of appendicitis, sore throat, mumps,acne, sebo-rheic dermatitis and various kinds of tumors, such as tumors of digestive tract,carcinoma of liver. It was reported that the MeOH extract of H. diffusa demonstrated a significantantitumor activity and ursolic acid succeeded in being isolated from the MeOH extract as an activecomponent . Shan BN, et al suggested that the direct aqueous extract of H. diffusa hadimmuno-modulating activity and antitumor activity in vitro through stimulating the immune system tokill or engulf tumor cells. But regarding anti-tumor activity in vivo of water soluble extracts fromH. diffusa, no detail was reported. Therefore, we prepared water soluble extracts (H_1 and H_2)from H. diffusa and evaluated their anti-tumor property in vivo experiments as well as protectiveeffect on chemo-therapeutic damage.

Anti-tumor Effects of a Recombinant Fowlpox Virus Expressing Apoptin on Human Cervical Carcinoma in Vivo and in Vitro

Apoptin is a chicken anemia virus-derived,p53-independent,bcl-2-insensitive apoptotic protein with the ability to specifically induce apoptosis of various human tumor cells,but not of normal diploid cells.To explore the application of apoptin in tumor gene therapy,we used a recombinant fowlpox virus expressing apoptin protein （vFV-Apoptin） to investigate the anti-tumor effectes of vFV-Apoptin on human cervical carcinoma（HeLa） cells in vivo and in vitro through 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide（MTT） assay,acridine orage/ethidium bromide（AO/EB） and annexin V staining test,respectively.The results show that vFV-Apoptin inhibites the proliferation of HeLa cells in vitro through inducing the apoptosis of HeLa cells,and the inhibition effect of vFV-Apoptin has a dose-effect and time-effect relationship.The results of animal models show that vFV-Apoptin significantly inhibits tumor growth,extends the lifespan of animals and improves the mean survival.Experimental results indicate that vFV-Apoptin has a potential application in the tumor gene therapy.

Enhanced Anti-tumor Effect of an IFN-γ-EGF Fusion Protein

The novel fusion proteins harbering human or mouse interferon combined with epidermalgrowth factor receptor binding domain were constructed using methods of genetic and proteinengineering. The fusion proteins were assayed to retain complete antiviral activities. The EGFreceptor binding moiety of the fusion proteins exhibited competitive binding saainst 125 I-EGFfor EGF receptbrs on A431 cells. The fusion proteins were shown to be more potent in in-hibiting the growth of cultured target carcinoma cells than interferon-y alone. Experimentaldata derived from rnouse Bl6 malignant melanoma models indicates that the weight of tumorin mice treated with IFN fusion proteins was significantly smaller than that of mice treatedwith interferon-y alone. The work here is unprecedented in the world and provides a reliableevidence to supPOrt the upcoming clinical employment of a class of interferons that specificallytarget tumor cell

Valproic Acid Enhances the Anti-tumor Effect of(-)-gossypol to Burkitt Lymphoma Namalwa Cells

Burkitt lymphoma is a highly aggressive B-cell neoplasm. New therapeutic methods are needed to overcome the adverse effect of intensive chemotherapy regimens. Valproic acid and （-）-gossypol are two kinds of chemical compounds used as new anti-tumor drugs in recent years.

Anti-tumor Effect and Mechanism of SEA-Fab’ Coupled Protein on Gastric Tumor

Summary： The anti-tumor effect and mechanism of SEA-Fab＇ coupled protein on gastric tumor was studied. The target cell Walke-256 was treated with SEA-Fab＇ synthesized chemically or SEA respectively for 24 h, 36 h or 72 h. PBMC＋Walke-256 cells served as controls. The apoptotic index of SEA-Fab＇ against effector cells was detected. In the mouse gastric cancer models （n=60）, SEA-Fab＇, SEA and normal saline was injected in experimental group, SEA group and control group respectively. The occurrence and weight of tumor was observed. The results showed that the apoptotic index was significantly higher in the SEA-Fab＇ （34.6 -68.9%） and SEA group （15.5-31.9%） than in PBMC＋Walker-256 group （5.5%-12.8%） with the difference being significant （P〈0.01）. And there was significant difference between SEA-Fab＇ group and SEA group （P〈0.01）. The tumor weight in SEA-Fab＇, SEA and control groups was 3.6±0.53 g, 0. 78±0. 26 g and 0.49±0. 17 g respectively with the difference being statistically significant between the SEA-Fab＇ group, SEA group and the control group （P〈0.01）. In the SEA-Fab＇s and SEA groups, there were CD4^＋ T and CD8^＋ T cell infiltrates, but in the cotnrol group, no or few T lymphocytes were seen in the mouse tumor tissue. It was concluded that SEA-Fab＇ was more effective to activate T lymphocytes to kill the tumor cells than SEA used alone. It was feasibility by using the monoclonal antibody as carrier to perform the targeted Immunotherapy of gatric tumor.

Combined anti-tumor effects of mDRA-6 and nimesulide on human hepatocellular cancer cell line SMMC-7721

Objective: The aim of this work was to evaluate anti-tumor effects of mDRA-6 plus nimesulide on a human hepatocellular cancer cell line, SMMC-7721, and study the main mechanisms. Methods: The DR5 receptor of SMMC-7721 cells was detected by flow cytometry (FCM). For further experimental application, SMMC-7721 cells were treated with proper dose of mDRA-6, nimesulide, or mDRA-6 plus 200 μmol/L nimesulide; untreated SMMC-7721 cells were comparably set as control. Cytotoxicity was tested by MTT assay; cell morphology was examined using Hoechst 33258 staining; and apoptosis was determined by FCM. Results: The positive rate of DR5 on SMMC-7721 was 95.0%. Either mDRA-6 or nimesulide alone induces SMMC-7721 cell death in a dose-dependent manner. Treatment of 1,600 ng/mL mDRA-6 for 12h led to a cell-death rate of 35.0%, while an increased cell-death rate (91.1%) was found under the same condition of mDRA-6 treatment supple- mented with 200 μmol/L nimesulide. Hoechst 33258 and Annexin V/PI staining confirmed apoptosis as the main cause of this anti-tumor response. Conclusion: Both mDRA-6 and nimesulide can induce apoptosis of SMMC-7721 cells, and they have synergistic anti-tumor activities against SMMC-7721.

Activity Screening Study on the Anti-tumor Effects of Extracts from Mahoniae caulis

[Objectives]To explore the anti-tumor activity of the extracts of petroleum ether,ethyl acetate,n-butanol and aqueous solution from Mahoniae caulis.[Methods]The extracts were extracted with petroleum ether,ethyl acetate,n-butanol and aqueous solution respectively,and then concentrated.The inhibitory effects of these extracts on the growth of three tumor cell lines in vitro were detected by CCK-8 method,and the IC 50 value was calculated.[Results]The four extracts inhibited the growth of the three tumor cell lines in vitro,among which the n-butanol extract had the best anti-tumor activity.The IC 50 values of the n-butanol extract on human gastric cancer(SGC-7901),human breast cancer(MCF-7)and human liver cancer(BEL-7404)cell lines were 0.23,0.25 and 0.58 mg/mL,respectively.[Conclusions]The ethanol extract of Mahoniae caulis under petroleum ether,ethyl acetate,n-butanol and aqueous solution had certain anti-tumor effect,and n-butanol extract had the best anti-tumor activity.

Anti-tumor effect of matrine combined with cisplatin on rat models of cervical cancer

Objective:To observe the anti-tumor effect of matrine combined with cisplatin on U14 rat models of cervical cancer.Methods:A total of 80 female Kunming rats were used to establish U14 rat models of cervical cancer and then divided into groups Ⅰ,Ⅱ,Ⅲ and Ⅳ,with 20 rats in each.For Group Ⅰ,the control group,injection of normal saline was given around the tumors.For Group Ⅱ,injection of 2 mg/kg cisplatin was given around the tumors.For Group Ⅲ,injection of 75 mg/kg matrine was given around the tumors while the combined injection of matrine and cisplatin was given for Group Ⅳ with the same doses as Groups Ⅱand Ⅲ.The animals were sacrificed 10 d after the injection and tumors were taken out for the comparisons of tumor weights after injection and calculation of anti-tumor rates,while thymus and spleen were taken for thymus index and spleen index.Blood in eyeball was collected for determination of changes in serum creatinine and urea nitrogen levels.Sections of tumor issue were prepared and morphological changes in tumor tissue cells were observed by using immunohistochemistry technique.Results:After injection,the thymus index and spleen index in Groups Ⅲ and Ⅳ were significantly higher than those in Groups Ⅰ and Ⅱ(P<0.05)while the two indexes in Group Ⅱ were significantly lower than Group Ⅰ(P<0.05).The tumor weights in Groups Ⅱ and Ⅳ were significantly smaller than those in Groups Ⅰ and Ⅲ(P<0.05) with significantly higher anti-tumor rates than Groups Ⅰ and Ⅲ(P<0.05).The serum creatinine and urea nitrogen levels in Groups Ⅲ and Ⅳ were significantly lower than Group Ⅱ(P<0.05) and the two indicators in Group Ⅲ were significantly lower than those in Group Ⅳ(P<0.05).The observation under the histological microscope showed densely arranged tumor cells in Group Ⅰ,growing as a crumby structure and diffuse appearance,with hyperchromatic and large nuclei,and abundant cytoplasm.In the case of Group Ⅱ,it showed less tumor cells,with extensive degenerative necrosis,sparse arrangement and karyopyknosis as well as karyoclasis.For Group Ⅲ,necrosis of tumor cells in different sizes and heterogeneous color in nuclei were observed.For Group Ⅳ,the number of tumor cells was significantly smaller than Groups Ⅰ and Ⅲ and the tumor cells presented an appearance of crumby structure as cancer nests,with more proliferation of connective tissue.Conclusions:The treatment of matrine combined with cisplatin can significantly improve the anti-tumor effect on U14 rats with cervical cancer,which can be a new option for the treatment for cervical cancer.

Research Progress of Anti-tumor Effects of Curcuma zedoaria and its Active Ingredients Through Immune Regulation Mechanism

The continuous increase in the incidence rate of various fatal malignant tumors in the recent years warrants an imperative search for medications or drugs with obvious anti-tumor eflects and reliable curative effects.Previous studies have found that Curcuma zedoaria and its active ingredients,such as turmeric oil,curcumol,and P-elemene,have obvious antitumor effects,and they do not have the adverse reactions and side effects seen in the anti-tumor drugs of Western medicine.Based on the review and inductive analysis of related literature,we summarize in the present article the results of some researchers who investigated the anti-tumor effects of Curcuma zedoaria and its active ingredients through the immune regulation mechanism.

Anti-tumor effects of p53N15-based fusion peptide in the transfected H1299 lung cancer cells

Objective Loss-of-function mutation of p53,a tumor suppressor gene,is an important mechanism for the development of human cancers. In this study we tried to transfect p53N15-based fusion peptide into H1299,a lung cancer cell line,and evaluate the anti-tumor effects of the fusion peptide. Methods Adeno-associated virus (AAV) vectors were used for transfecting p53N15 fusion peptide into p53-null lung adenocarcinoma H1299 cells.

Anti-tumor effects induced by gene vaccines co-expressing truncated human prostate specific membrane antigen gene and mouse 4-1BBL

Objective To investigate the influence of m4-1BBL on anti-tumor effects induced by truncated human prostate specific membrane antigen ( tPSMA ) gene in mice. Methods A eukaryotic expression plasmid encoding tPSMA and m4-1BBL ( pDC316-tPSMA-IRES m4-1BBL) ,pDC316-tPSMA and pDC316 were constructed.

Screening of Anti-tumor Effective Extracts from Sedum bulbiferum Makino and HPLC Determination of Quercetin and Kaempferol in This Herbal Medicine

[Objectives] To investigate the anti-tumor activity of Sedum bulbiferum Makino in vitro,and establish a HPLC method for determination of quercetin and kaempferol in S. bulbiferum. [Methods] The inhibitory activities of different extracts and total flavonoids of S. bulbiferum on proliferation of three kinds of cancer cells( Hep G2,EC109,SW480) were tested by MTT assay. HPLC method for determination of quercetin and kaempferol in S. bulbiferum was established. [Results]The growth and proliferation of the three kinds of cancer cells were all significantly inhibited by ethyl acetate fraction and total flavonoids isolated from S. bulbiferum. With each extraction concentration increasing,stronger anti-tumor activity was found. The linear ranges of quercetin and kaempferol were 0. 03-0. 36 μg( R = 0. 999 9) and0. 08-0. 96 μg( R = 0. 999 9),and the average recoveries were 98. 90%( RSD = 1. 15%) and 98. 27%( RSD = 1. 70%),respectively.[Conclusions]S. bulbiferum has significant anti-tumor activity in vitro. The HPLC method established was accurate,reproducible,and could be used for quality control of this crude drug.

Anti-tumor effect of statin on pancreatic adenocarcinoma:From concept to precision medicine

A statin is a cholesterol-lowering agent,which inhibits HMG-CoA(3-hydroxy-3-methylglutaryl-coenzyme A)reductase and subsequently reduces the cholesterol precursor,and was first used commercially in 1987.The concept of cholesterol restriction leading to cancer cell dysfunction was proposed in 1992.The interruption of different signaling pathways has been proved in preclinical experiments to elucidate the anti-tumor mechanism of statins in pancreatic adenocarcinoma.Observational studies have shown that the clinical use of statins is beneficial in patients with pancreatic adenocarcinoma,including a chemoprevention effect,post-surgical resection follow-up and therapeutic prognosis of advanced cancer stage.Arrest of the cancer cell cycle by the combined use of gemcitabine and statin was observed in a cell line study.The effect of microbiota on the tumor microenvironment of pancreatic adenocarcinoma is a new therapeutic approach as statins can modulate the gut microbiota.Hence,further randomized trials of statins in pancreatic adenocarcinoma treatment will be warranted with application of precision medicine from microbiota-derived,cell cycle-based and signaling pathway-targeted research.

Anti-tumor Effects of Aspirin: Progress in Clinical and Basic Studies

Beyond the antipyretic analgesic and anti-inflammatory effects for which aspirin has historically been used,studies have shown that aspirin also plays an important role in the prevention or treatment a variety of diseases.The anti-tumor effects of aspirin have received increasing attention during the past decade.Many studies have explored the molecular mechanisms underlying these anti-tumor effects in vitro and in vivo,and abundant discoveries have been made through observational or interventional clinical studies.In terms of its molecular function,aspirin has been shown to prevent tumor cell growth through inhibiting the signal transduction of the COX,tumor necrosis factor-related apoptosis-inducing ligand(TRAIL),NFκB/IκB,and Bcl-2/Bax pathways.Under certain conditions,aspirin can also induce autophagy,which is an inhibitory mechanism for some tumors.This article provides a comprehensive overview of the anti-tumor effects of aspirin and discusses the concrete mechanisms underlying aspirin’s anti-tumor effects that have been discovered in the past 30 years.

Research Progress in Anti-tumor Effects of Traditional Chinese Medicine and Its Extracts

Traditional Chinese medicine and its extracts have received widespread attention due to their significant anti-tumor effects and low adverse reactions.Many traditional Chinese medicine and its extracts have been applied in clinical tumor treatment.In this paper,the research progress in anti-tumor effects of plant-based traditional Chinese medicine and its extracts,animal-based traditional Chinese medicine and its extracts,and traditional Chinese medicine compound is reviewed.

Hematopoiesis reconstitution and anti-tumor effectiveness of Pai-Neng-Da capsule in acute leukemia patients with haploidentical hematopoietic stem cell transplantation

BACKGROUND With the rapid development of haploidentical hematopoietic stem cell transplantation(haplo-HSCT),primary poor graft function(PGF)has become a lifethreatening complication.Effective therapies for PGF are inconclusive.New Chinese patent medicine Pai-Neng-Da(PND)Capsule exerts dual effect in promoting hematopoiesis recovery and regulating immunity.Still,the application of PND capsule in hematopoietic stem cell transplantation,especially in the haplo-HSCT setting,has not yet been reported.AIM To evaluate the role of PND capsule in acute leukemia patients with haplo-HSCT.METHODS We retrospectively collected data of acute leukemia patients who underwent haplo-HSCT at the Affiliated People’s Hospital of Ningbo University between April 1,2015 and June 30,2020.Twenty-nine consecutive patients received oral PND capsule from the sixth day to the first month after haplo-HSCT were included in the PND group.In addition,31 patients who did not receive PND capsule during haplo-HSCT were included in the non-PND group.Subsequently,we compared the therapeutic efficacy according to the western medical evaluation indexes and Chinese medical symptom scores,and the survival between the PND group and the non-PND group,using the chi-square test,Fisher’s exact test,and the Kaplan-Meier method.RESULTS The duration of platelet engraftment was shorter in the PND group than in the non-PND group(P=0.039).The PND group received a lower frequency of red blood cells and platelet transfusions than the non-PND group(P=0.033 and P=0.035,respectively).In addition,PND capsule marginally reduced the rate of PGF(P=0.027)and relapse(P=0.043).After 33(range,4-106)months of follow-up,the 3-year relapse-free survival(P=0.046)and progression-free survival(P=0.049)were improved in the PND group than in the non-PND group.Also,the therapeutic efficacy of the PND group according to Chinese medical symptom scores was significantly better than that of the non-PND group(P=0.022).Moreover,the adverse events caused by PND capsule were mild.Nevertheless,there were no significant differences in the duration of neutrophil engraftment,the risk of infection within 100 days after haplo-HSCT,the acute graft-versus-host disease,or the 3-year overall survival between the two groups.CONCLUSION PND capsule could promote hematopoiesis reconstitution,improve the therapeutic efficacy of Chinese medical symptom scores,present anti-tumor effectiveness,and prolong the survival of acute leukemia patients with haplo-HSCT.

Immunoregulation and anti-tumor effects of Polyporusus Bellatus： a review of recent research

Background： We summarized the Polyporusus Bellatus （PPS） efficacy of immunomodulation, liver protection and anti-tumor, then provide scientific basis for further research and clinical application. This dissertation first overview relevant literatures of PPS recent years and describe comprehensively the research progress of the immunoregulation, liver protection and anti-tumor effects and mechanism of PPS. The review shows that the PPS play anti-tumor effects through antioxidation, scavenging free radicals, inhibiting tumor cell proliferation, inducing apoptosis, affecting tumor gene expressions and enhancing immune functions. PPS can exert immunoregulatory, hepatoprotective and anti-tumor effects through multiple pathways and multiple targets, which provides a good application prospect in clinic.