Purification,structural elucidation,and in vitro antitumor effects of novel polysaccharides from Bangia fuscopurpurea

A water-soluble polysaccharide,designated BFP-3,was isolated from Bangia fuscopurpurea by hot water extraction,anion-exchange,and size-exclusion chromatography and tested to determine its antitumor activity.The structural characteristics of BFP-3 were investigated by chemical and spectroscopic methods,including partial acid hydrolysis,methylation analysis,one-and two-dimensional nuclear magnetic resonance,and gas chromatography-mass spectrometry.The results showed that BFP-3 was mainly comprised of rhamnose,arabinose,mannose,glucose,and galactose.Moreover,the weight-average molecular weight of BFP-3 was estimated to be approximately 333 kDa.The backbone of BFP-3 was primarily composed of repeating 5-α-l-Araf-1→(4-α-d-Glcp-1)_(4)→4,6-β-d-Manp-1 units,and the side chains consisted of repeatingβ-d-Galp-1→(4-β-d-Galp-1)_(4)→4,6-β-d-Galp-1→3,4-α-l-Rhap,β-l-Arap-1→(3-β-d-Galp-1)_(3),andβ-l-Arap-1 units.Counting Kit-8 assays revealed that BFP-3 significantly inhibited the proliferation of A2780,COC1,SKOV3,HO-8910,and OVCAR3 ovarian cancer cells in vitro,indicating that BFP-3 could have potential applications in the treatment of ovarian cancer.

Study on the Antitumor Effects of Low-energy Laser Irradiation Combined with Cyclophosphamide

Systematic experiments about the antitumor effects of low energy laser irradiation combined with the traditional antitumor medicine of cyclophosphamide were conducted using the experimental model of mouse S180 ascites sarcoma.The three groups of tumor bearing mice were irradiated upon the inner corners with the dosages of 11 00,14 67 and 22 00 J·cm -2 LELI respectively,and injected with CYT intraperitoneally to observe the changes of the survival time,the ascites growth speed,and the kinetic changes of immune functions.The survival times of the three groups of CYT/LELI combination were obviously longer than those of the tumor and CYT control groups.Correspondingly,the amounts of ascites,tumor cells densities and total tumor cells in CYT/LELI groups decreased significantly,while the death ratio of the tumor cells increased.Comparatively,the group of 22 00 J·cm -2 LELI combined with CYT showed the most ideal antitumor effects,and the life prolongation ratio was up to 53 20%.

ANTITUMOR EFFECTS OF WICK OF SUN-FLOWER STEM IN MICE

A well-known Chinese traditional drug, decoction of wick of sun-flower stem, has been used to treat cancer and certain other diseases.1,2 Animal experiments in mice showed that transplantation of Sarcoma 180 (S180) and of Uterus cervical cancer 14 (U14) were signlflcanly inhibited by this decoction. The Inhibition rates of tumor weight were 33 -81 % and in about 6 - 20% of treated mice, complete tumor regression has been demonstrated. So tar no acute toxic side-effect was noted. This is in contrast to most of the antitumor chemltherapeutic drugs known to produce different degrees of toxlcity or induce Immunosuppression as a side effect. For this reason, we have undertaken the present study.

ANTITUMOR EFFECT OF ACTINIDIA CHINENSIS POLYSACCHARIDE ON MURINE TUMOR

A new polysaccharide compound (ACPS-R) has recently been isolated from the root of Actinidia Chinensis Planch. When given inttaperitoneally to the transplantable tumor bearing mice at dose of 75-125 mg/kg, the tumor inhibition rate was more than 88.8% in Ehrilich ascitic cancer (EAC) or ascitic from of hepatoma (HepA) and more than 49.6% in solid hepatoma (HepS). The treatment effect of ACPS-R on EAC at dose of 80-100 mg kg and 125 mg/kg were comparable to that of cyclophosphamide at dose of 15 mg/kg and 22.5 mg/kg, respectively. ACPS-R could also prolong the life of EAC- or P388-bearing mice, and increase the percentage of EAC-free mice. In addition, when ACPS-R was used in combination with 5-Fu, the antitumor effect was enhanced as compared with 5-Fu alone. A marked increase in cAMP levels end cAMP cGMP ratio of spleen of EAC-bearing mice were observed after treatment of ACPS-R. The increase of both para meters nearly reached the normal levels of healthy mice. The increases of cAMP, cAMP cGMP and tumor remission had statistical significance. It showed an intermediate inhibitory effect of ACPS-R on DNA synthesis by incorporating 3H-TdR into EAC cells.The results indicated that ACPS-R acts as a new antitumor polysaccharide, and the treatment effect of Actinidia root in folk medicine is probably related to ACPS-R.

Systematic literature review of the antitumor effect of octreotide in neuroendocrine tumors

AIM To provide a comprehensive examination of the existing evidence of the antitumor effect of long-acting octreotide in neuroendocrine tumors(NETs).METHODS A systematic literature review of clinical trials and observational studies was conducted in PubM ed, EMBASE, and Cochrane through January 18, 2017. Conference abstracts for 2015 and 2016 from 5 scientific meetings were also searched.RESULTS Of 41 articles/abstracts identified, 13 unique studies compared octreotide with active or no treatment. Two of the 13 studies were clinical trials; the remaining were observational studies. The phase 3 Placebo-Controlled, Double-Blind, Prospective, Randomized Study of the Effect of Octreotide long-acting repeatable(LAR) in the Control of Tumor Growth in Patients with MetastaticNeuroendocrine Midgut Tumors clinical trial showed that long-acting octreotide significantly prolonged time to tumor progression compared with placebo in patients with functionally active and inactive metastatic midgut NETs; no statistically significant difference in overall survival(OS) was observed, possibly due to the crossover of placebo patients to octreotide. Retrospective observational studies found that long-acting octreotide use was associated with significantly longer OS than no octreotide use for patients with distant metastases although not for those with local/regional disease. CONCLUSION The clinical trial and observational studies with informative evidence support long-acting octreotide's antitumor effect on time to tumor progression and OS. This review showed the rarity of existing studies assessing octreotide's antitumor effect and recommends that future research is warranted.

Antitumor and synergistic effect of Chinese medicine “Bushen huayu jiedu recipe” and chemotherapy on transplanted animal hepatocarcinoma

AIM： To investigate the antitumor and synergistic effect of Chinese medicine “Bushen huayu jiedu recipe” （recipe for invigorating the kidney, removing blood stasis and toxic substances） and chemotherapy on mice hepatocarcinoma. METHODS： Bushen huayu jiedu recipe （BSHYJDR） consisting of Chinese Cassia Bark, Psoralea, Zedoary, Rhubarb, etc. is equal to 1.5 g/mL liquid of originated herbs after being decoded, filtered, and concentrated. Kunming mice, weighing 18-22 g, were injected with 0.2 mL ascitic hepatocarcinoma H22 containing 1 × 10^7 cells/mL into armpit of the right forelimb of mice. After 24 h, the mice were weighed and randomly divided into tumor-bearing model control group, cisplatin （DDP） group, BSHYJDR high dosage group, low dosage BSHYJDR group, DDP combined with high and low dosage BSHYJDR group, 10 mice in each group. DDP group received injection intraperitoneally （ip） at the dosage of 1 mg/kg （equal to 1/10 LD50）, once a day for 4 d. High and low dosage BSHYJDR groups received intragastric BSHYJDR at the dosages of 26.6 and 13.3 g/kg （20 and 10 times each of clinical adult dosage） respectively, while tumor-bearing model group received the equal volume of distilled water once a day for 10 d. On the 11^th d, the mice were weighed and killed, then the tumor was dissected and weighed, the repression rate （RR） was calculated according to the mean weight of tumor （MWT）. RESULTS： Compared to the model group （MWT： 1.30±0.73）, DDP group （MWT： 0.41±0.09, RR： 68.46%） had a significant difference in the inhibition of hepatocarcinoma H22 （P〈0.01）. High dosage BSHYJDR group （MWT： 0.69±0.29, RR： 46.92%） also had a significant difference in inhibition （P〈0.05）, while no difference was found in low dosage BSHYJDR group （MVVT： 0.85±0.34, RR： 34.62%） （P〉0.05）. When DDP was combined with high dosage BSHYJDR （MWT： 0.29±0.17, RR： 77.69%） and low dosage BSHYJDR （MWT： 0.38±0.21, RR： 70.77%） respectively, we could see improvement of the inhibition effect of DDP on transplanted hepatocarcinoma H22. DDP combined with high dosage BSHYJDR had a significant difference （P〈0.001） compared to DDP, while DDP combined with low dosage BSHYJDR only had a little improvement that is not remarkable. CONCLUSION： Chinese medicine BSHYJDR in combination with chemotherapy can inhibit transplanted hepatocarcinorna in mice.

Enhancement of Antitumor Effect of Tegafur/Uracil(UFT) plus Leucovorin by Combined Treatment with Protein-Bound Polysaccharide,PSK,in Mouse Models

We evaluated the antitumor effect of combined therapy with tegafur/uracil （UFT） plus leucovorin （LV） （UFT/LV） and protein-bound polysaccharide, PSK, in three mouse models of transplantable tumors. UFT/LV showed antitumor effect against Meth A sarcoma, and the antitumor effect was enhanced when PSK given concomitantly. UFT/LV showed antitumor effect to Lewis lung carcinoma and PSK alone also showed antitumor effect at high dose, but a combination of UFT/LV and PSK resulted in no enhanced antitumor effect. Colon 26 carcinoma was weakly responsive to UFT/LV, and no enhancement of antitumor effect was found even PSK was used in combination. In conclusion, while the effect of PSK varies depending on tumor, combined use of UFT/LV and PSK may be expected to augment the antitumor effect.

Antitumor Effects of Ethanol Extract from Ventilago leiocarpa Benth on Sarcoma 180 Tumor-Bearing Mice and Possible Immune Mechanism

Objective To explore the antitumor effects of ethanol extract from Ventilago leiocarpa Benth(EEVLB)on sarcoma 180(S180)tumor-bearing mice and the potential mechanism.Methods Sixty mice were randomly assigned to 6 groups according to a random number table:normal group,model group,5-fluorouracil(5-FU)group(0.02 g·kg^(−1)),and high-,medium-,low-dose EEVLB groups(100,84,and 56 g of raw material·kg^(−1)body weight,respectively),with 10 mice each group.All treatments were given once daily for 10 consecutive days.Effects of EEVLB on inhibiting tumor growth and immune function in mice were evaluated among all groups after the treatments by detecting tumor inhibition rate,organ index,serum levels of interleukin(IL)-2,-6,-10,CD3^(+)CD4^(+)T lymphocytes,CD4^(+)/CD8^(+)ratio,caspase-3 and Bcl-2.Results EEVLB with different concentrations achieved inhibition of tumor growth in vivo,wherein the high-dose group showed the most significant reduction in tumor weight and increased apoptosis of tumor cells(P<0.05).In addition,both net weight gain and spleen index of mice showed uptrend in EEVLB treatment groups(P<0.05).Besides,serum levels of IL-2 and IL-6,percentages of CD3^(+)CD4^(+)T lymphocytes and ratio of CD4^(+)/CD8^(+)in peripheral blood were elevated in high-and medium-dose EEVLB groups compared with the model group(P<0.05).Also,upregulation of caspase-3 and downregulation of Bcl-2 were observed at protein levels in the high-dose EEVLB group(P<0.01).Conclusions EEVLB exhibits promising antitumor activity in vivo.This effect might be due to activation of apoptotic signaling pathway,increase of cytokine levels and enhancement of immune function in tumor-bearing mice.

In vitro antitumor effect of cucurbitacin E on human lung cancer cell line and its molecular mechanism

Cucurbitacin E(CuE) is previously reported to exhibit antitumor effect by several means.In this study, CuE acted as a tyrosine kinase inhibitor interfering with the epidermal growth factor receptor/mitogen-activated protein kinase(EGFR/MAPK) signaling pathway and subsequently induced apoptosis and cell cycle arrest in non-small-cell lung cancer(NSCLC) cell line A549.The apoptosis regulators, cleaved Caspases-3 and Caspases-9, were observed to be increased with the treatment of CuE.The activated transcription factor STAT3 and the apoptosis inhibitor protein survivin were also observed to be reduced.The cell cycle regulators, CyclinA2, cylinB1, CyclinD1 and CyclinE, were also investigated and the results suggested that the cell cycle was arrested at G1/G0 phase.Treatment of CuE also altered the existence status of most of the participants in the EGFR/MAPK signaling.Phosphorylation of EGFR enhanced significantly, leading to the alteration of members downstream, either total amount or phosphorylation level, notably,MEK1/2 and ERK1/2.Moreover, the results of molecular simulation brought an insight on the interaction mechanism between CuE and EGFR.In summary, CuE exhibited anti-proliferative effect against A549 cells by targeting the EGFR/MAPK signaling pathway.

PLASMID VACCINE ENCODING HN GENE FROM NEWCASTLE DISEASE VIRUS HAS MARKED ANTITUMORAL EFFECT IN VITRO

Objective: To explore the antitumor effects of hemaagglutinin-neuraminase gene (HN gene) from Newcastle disease virus. Methods: Plasmid vaccine of pIRHN was constructed and transfected into HeLa cells. The expression of HN was analyzed by Western blot analysis, and the mode of cell death was detected by fluorescence microscope, gel electrophoresis and TUNEL assay and the expression of p53 and bcl-2 was also analyzed in transfected Hela cells. The effect of pIRHN on sialic acid contents in the Hela cell was examined. Results: pIRHN nucleic acid vaccines could be expressed in eukaryotic cell. pIRHN could induce apoptosis after HeLa cells were transfected. The effect of antitumor responses of pIRHN was correlated with the contents of sialic acid in tumor cells, and there was no prominent evidence for the relatedness of the antitumor effect with the expression of p53 and bcl-2. Conclusion: pIRHN may become a new antitumor biological agent.

EFFECT OF ANTITUMOR DRUGS ON THE ACTIVITY OF DNA TOPOISOMERASE I

The activity of DNA topoisomerase Ⅱ prepared from either normal or tumor tissues were compared. It was found that the unknotting activity of the enzyme in malignant tumor cells was higher than that in normal cells. We selected some antitumor drugs including Chinese traditional medicine, and observed their effects on the unknotting activity of topoisomerase Ⅱ. The results showed that inhibition of the unknotting activity of the enzyme required very low concentrations of drugs, but much higher concentrations were required for other tested. Some antitumor drugs had no effect on the enzyme were also proved. It is interesting that carrageenan, an antiviral drug, strongly blocked the unknotting activity although its antitumor activity has not been reported.

THE ANTITUMOR ACTIVITY OF LYMPHOTOXIN AND THE EFFECT OF INTERLEUKIN-2 ON ITS FUNCTION

The effect of lymphotoxin (LT)-containing supernatant produced by lectin-stimulated human lymphocytes on tumor cells and the relation between interleukin-2 (IL-2) and LT were studied in this article. Results showed that LT-containing superna-tants had cytotoxicities on many different kinds of tumor cells from human and mice, that actinomycin D increased the LT activities on target cells and that IL-2 had the ability to increase the cytotoxicity of human PBMC on tumor cells, after being treated with LT, the target cells were more easy to kill by PBMC as well.

Inhibitory effect of acetylshikonin on human gastric carcinoma cell line SGC-7901 in vitro and in vivo

AIM:To investigate the inhibitory effect of acetylshikonin on human gastric carcinoma cell line SGC-7901 and its mechanism. METHODS:MTT assay was used to assess the inhibitory effect of acetylshikonin on proliferation of SGC-7901 cells.Apopt osis-inducing effect was determined by flow cytometry and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling with Hoechst staining.Expression of mRNA and protein in Bcl-2 and Bax was analyzed by reverse transcription-polymerase chain reaction and Western blot.Antitumor effect of acetylshikonin on a mouse SGC-7901 model was also determined. RESULTS:Forty-eight hours after treatment with acetylshikonin,MTT assay showed that acetylshikonin inhibited the proliferation of SGC-7901 cells in a dose-dependent manner.The half maximal inhibitory concentration of acetylshikonin to SGC-7901 cells was 0.428±0.07 mg/L.Cell shrinkage,nuclear pyknosis and chromatin condensation,which are the characteristics of cell apoptosis,were observed in treated SGC-7901 cells and the percentage of apoptosis increased in a dose-dependent manner.Acetylshikonin downregulated the expression of Bcl-2 and up-regulated the expression of Bax in the treated SGC-7901 cells compared with the controls.The experiment in vivo showed that 0.5,1,and 2 mg/kg of acetylshikonin significantly inhibited the growth of tumor in the mouse SGC-7901 model,with an inhibitory rate of 25.00%-55.76%. CONCLUSION:Acetylshikonin inhibits the growth of SGC-7901 cells in vitro and in vivo by inducing cell apoptosis.

Preparation, characterization, pharmacokinetics and anticancer effects of PEGylated β-elemene liposomes

Objective:This study aimed to develop a new polyethylene glycol(PEG)ylatedβ-elemene liposome(PEG-Lipo-β-E)and evaluate its characterization,pharmacokinetics,antitumor effects and safety in vitro and in vivo.Methods:The liposomes were prepared by ethanol injection and high-pressure micro-jet homogenization.Characterization of the liposomes was conducted,and drug content,entrapment efficiency(EE),in vitro release and stability were studied by ultra-fast liquid chromatography(UFLC)and a liquid surface method.Blood was drawn from rats to establish the pharmacokinetic parameters.The anticancer effect was evaluated in a KU-19-19 bladder cancer xenograft model.Histological analyses were performed to evaluate safety.Results:The PEG-Lipo-β-E showed good stability and was characterized as 83.31±0.181 nm in size,0.279±0.004 in polydispersity index(PDI),-21.4±1.06 mV in zeta potential,6.65±0.02 in pH,5.024±0.107 mg/mL inβ-elemene(β-E)content,and 95.53±1.712%in average EE.The Fourier transform infrared spectroscopy(FTIR)and differential scanning calorimetry(DSC)indicated the formation of PEG-Lipo-β-E.Compared to elemene injection,PEG-Lipo-β-E demonstrated a 1.75-fold decrease in clearance,a 1.62-fold increase in half-life,and a 1.76-fold increase in area under the concentration-time curves(AUCs)from 0 hour to 1.5 hours(P<0.05).PEG-Lipo-β-E also showed an enhanced anticancer effect in vivo.Histological analyses showed that there was no evidence of toxicity to the heart,kidney,liver,lung or spleen.Conclusions:The present study demonstrates PEG-Lipo-β-E as a new formulation with ease of preparation,high EE,good stability,improved bioavailability and antitumor effects.

The Inhibitory Effect of Oridonin on the Growth of Fifteen Human Cancer Cell Lines

OBJECTIVE To study the inhibitory effect of oridonin on the growth of cancer cells. METHODS Fifteen human cancer cell lines were subjected to various concentrations of oridonin in culture medium. The inhibitory rate of cell growth was measured by the MTT assay, and compared with a negative control and 5-Fu-positive control. RESULTS The 50% inhibiting concentration （IC50） and maximal inhibition （Imax） of oridonin shown by studying the growth of the cancer cell lines were as follows： leukemias （HL60 cells： 3.9 μg/ml and 73.8%, K562 cells： 4.3 μg/ml and 76.2%）; esophageal cancers（SHEEC cells： 15.4 μg/ml and 99.2%, Eca109 cells： 15.1 μg/ml and 84.6%, TEl cells： 4.0 μg/ml and 70.2%）; gastric cancers （BGC823 cells： 7.6 μg/ml and 98.7%, SGC7901 cells： 12.3 μg/ml and 85.7%）; colon cancers （HT29 cells： 13.6 μg/ml and 97.2%, HCT cells： 14.5 μg/ml and 96.5%）; liver cancers （Bel7402 cells： 15.2 μg/ml and 89.2%, HepG2 cells： 7.1 μg/ml and 88.3%）; pancreatic cancer （PC3 cells： 11.3 μg/ml and 68.4%）; lung cancer （A549 cells： 18.6 μg/ml and 98.0% ）; breast cancer （MCF7 cells： 18.4 μg/ml and 84.7%）; uterine cervix cancer （Hela cells： 13.7 μg/ml and 98.5%）. CONCLUSION Oridonin had a relatively wide anti-tumor spectrum, and a relatively strong inhibitory effect on the growth of the 15 human cancer cells. Inhibitory effects were concentration dependent.

THE ANTICANCER EFFECT AND ANTI－DNA TOPOISOMERASE II EFFECT OF EXTRACTS OF CAMELLIA PTILOPHYLLA CHANG AND CAMELLIA SINENSIS

The cytotoxic effect of extract of camellia ptilophyllachang(ECPC) and extract of camellia sinensis(ECS) onHeLa cell line, poorly differentiated nasopharyngealcarcinoma cell line(CNE2) and gastric cancer cell line(MGC-803 ) in vitro was studied using MIT assay method.The results showed that ECPC and ECS possessed significantcytotoxic effect on above three cell lines. The anticancer testin mice showed that ECPC had marked inhibitory effectagainst Ehrlich solid carcinoma(ESC) with inhibition ratesof 17. 8 48. 3% and with inhibition rates of 28. 3-54. 5% against reticular cell sarcoma(L2), and that ECShad inhibition rates of 31 . 5 -49. 4 % against ESC and 35. 8- 50% against L2. These two extracts had only marginalinhibitory effect against sarcoma- 180. The unknottingactivity of DNA topoisomerase II was inhibited completelyby ECPC and ECS at the concentration of 50 μg/ mlsuggesting that DNA topoisomerase II might be a targetenzyme of these two extracts.

Excellent effects and possible mechanisms of action of a new antibody–drug conjugate against EGFR-positive triple-negative breast cancer

Background:Triple-negative breast cancer(TNBC)is the most aggressive subtype and occurs in approximately 15%–20%of diagnosed breast cancers.TNBC is characterized by its highly metastatic and recurrent features,as well as a lack of specific targets and targeted therapeutics.Epidermal growth factor receptor(EGFR)is highly expressed in a variety of tumors,especially in TNBC.LR004-VC-MMAE is a new EGFR-targeting antibody–drug conjugate produced by our laboratory.This study aimed to evaluate its antitumor activities against EGFR-positive TNBC and further studied its possible mechanism of antitumor action.Methods:LR004-VC-MMAE was prepared by coupling a cytotoxic payload(MMAE)to an anti-EGFR antibody(LR004)via a linker,and the drug-to-antibody ratio(DAR)was analyzed by HIC-HPLC.The gene expression of EGFR in a series of breast cancer cell lines was assessed using a publicly available microarray dataset(GSE41313)and Western blotting.MDA-MB-468 and MDA-MB-231 cells were treated with LR004-VC-MMAE(0,0.0066,0.066,0.66,6.6 nmol/L),and the inhibitory effects of LR004-VC-MMAE on cell proliferation were examined by CCK-8 and colony formation.The migration and invasion capacity of MDA-MB-468 and MDA-MB-231 cells were tested at different LR004-VCMMAE concentrations(2.5 and 5 nmol/L)with wound healing and Transwell invasion assays.Flow cytometric analysis and tumorsphere-forming assays were used to detect the killing effects of LR004-VC-MMAE on cancer stem cells(MDA-MB-468 and MDA-MB-231 cells).The mouse xenograft models were also used to evaluate the antitumor efficacy of LR004-VC-MMAE in vivo.Briefly,BALB/c nude mice were subcutaneously inoculated with MDA-MB-468 or MDAMB-231 cells.Then they were randomly divided into 4 groups(n=6 per group)and treated with PBS,naked LR004(10 mg/kg),LR004-VC-MMAE(10 mg/kg),or doxorubicin,respectively.Tumor sizes and the body weights of mice were measured every 4 d.The effects of LR004-VC-MMAE on apoptosis and cell cycle distribution were analyzed by flow cytometry.Western blotting was used to detect the effects of LR004-VC-MMAE on EGFR,ERK,MEK phosphorylation and tumor stemness marker gene expression.Results:LR004-VC-MMAE with a DAR of 4.02 were obtained.The expression of EGFR was found to be significantly higher in TNBC cells compared with non-TNBC cells(P<0.01).LR004-VC-MMAE inhibited the proliferation of EGFRpositive TNBC cells,and the ICvalues of MDA-MB-468 and MDA-MB-231 cells treated with LR004-VC-MMAE for 72 h were(0.13±0.02)nmol/L and(0.66±0.06)nmol/L,respectively,which were significantly lower than that of cells treated with MMAE[(3.20±0.60)nmol/L,P<0.01,and(6.60±0.50)nmol/L,P<0.001].LR004-VC-MMAE effectively inhibited migration and invasion of MDA-MB-468 and MDA-MB-231 cells.Moreover,LR004-VC-MMAE also killed tumor stem cells in EGFR-positive TNBC cells and impaired their tumorsphere-forming ability.In TNBC xenograft models,LR004-VC-MMAE at 10 mg/kg significantly suppressed tumor growth and achieved complete tumor regression on day 36.Surprisingly,tumor recurrence was not observed until the end of the experiment on day 52.In a mechanistic study,we found that LR004-VC-MMAE significantly induced cell apoptosis and cell cycle arrest at G/M phase in MDAMB-468[(34±5)%vs.(12±2)%,P<0.001]and MDA-MB-231[(27±4)%vs.(18±3)%,P<0.01]cells.LR004-VC-MMAE also inhibited the activation of EGFR signaling and the expression of cancer stemness marker genes such as Oct4,Sox2,KLF4 and EpCAM.Conclusions:LR004-VC-MMAE showed effective antitumor activity by inhibiting the activation of EGFR signaling and the expression of cancer stemness marker genes.It might be a promising therapeutic candidate and provides a potential therapeutic avenue for the treatment of EGFR-positive TNBC.

Progress on the Study of the Anti-Tumor Effect of Emodin

Cancer is a disease caused by the loss of normal cell regulation and excessive proliferation. At present, there are a lot of anticancer drugs, but most of them are not ideal, with sereve side effects. Besides, during the treatment, the patients feel very bad, and they are always in great pain. Emodin is a natural anthraquinone derivative found in a variety of herbal preparations. Many studies have shown that emodin has a significant therapeutic effect on lung cancer, liver cancer, breast cancer, and so on. After reviewing a large amount of literatures, this paper summarizes the research progresses of emodin anticancer in the past five years, in order to provide theoretical basis for further development and utilization of emodin and its metabolites.

Design,Synthesis and Synergistic Effects of Novel Derivatives of Solanesol

To further explore the biological activities of solanesylamine derivatives, several novel solanesylpiperazinotri-amines and their amides were designed and synthesized, the chemical structures of target compounds were confirmed by IR, ^1H NMR, MS, and element analysis. The in vitro antitumor activities of the synthetic compounds were as-sessed by MTT test on L1210 and CHO cells. The preliminary results showed that at low micromolar concentrations these compounds exhibit obvious toxicity against tumor cells, and the synergistic effect on clinical antitumor agent in-dicated that at noncytotoxic concentrations, they also evidently enhance the curative effect of vincristine（VCR）. The synergistic effects of compounds 4a, 4c, and 9 were even superior to that of reference compound N,N＇-bis（3,4-dime-thoxybenzyl） -N- solanesyl-ethylenediamine （ SDB ）.

Synthesis and Antitumor Activities In Vitro of Solanesylpiperazinotriamine

A series of novel antitumor agents-the solanesylpiperazinotriamine derivatives were designed and synthesized, their structures were confirmed by IR,^ 1H-NMR, MS, and element analysis. The preliminary tests showed that at low micromolar concentrations these compounds exhibited obvious toxicity on tumor cells in vitro, and the synergistic effect on clinical antitumor agent indicated that at noncytotoxic concentrations they also evidently enhanced the curative effect of vincristine.