| The gastric cancer is one of the most common tumor in Chine.Parkin,according to latest reports the current rate of its fourth place ranking,second only to lung cancer mortality rate is ranked second.Surgery is the main treatment,but because the majority of patients with varying degrees of the existence of micro-metastasis, postoperative recurrence and metastasis in patients with advanced gastric cancer is often clinically,so chemotherapy in the comprehensive treatment of gastric cancer in a very important position.Commonly used at home and abroad there is the efficiency of chemotherapy in 50%to 70%,but there are still a part of treatment failure in patients with gastric cancer.In recent years,studies show that the malignant cells to chemotherapeutic drug sensitivity of decline was the main reason for the impact of treatment.Teniposide(VM-26) are topoisomeraseⅡinhibitors,were used in the United States FDA approved the treatment of a variety of tumors.VM-26 through the inhibition mechanism of TopoⅡ,interfere with DNA double-strand breaks to be connected to the role,to prevent cell replication transcription function,the cell block at G2/M phase and induce apoptosis.The drug in clinical applications on a wide range.The drug due to the good permeability of the meninges,in small cell lung cancer,brain tumors,blood system,such as tumor and the treatment of lymphoma on the location of an important,but less reported aspects of gastric cancer.At the clinical treatment of gastric cancer in Henan Province People's Hospital,the first ontology VM-26,DDP,5-FU synergy of these three drugs have formed a United VDF treatment of advanced gastric cancer,there is the efficiency of 71%,and commonly used in EDF(VP-16+DDP+5-FU) program(48.8 percent efficiency),the difference was significant.Results of basic laboratory research to further explain the design of the VDF of the reasonable and scientific programs.Oxaliplatin and cisplatin chemotherapy for gastric cancer are first-line drugs, although these two drugs are the platinum category,the role of cell sites are DNA (L-OHP is also the role of RNA),but the two drugs without cross-resistance,and side-effects do not stack,referred to the two drugs have reported that there is synergy, but the two drugs are combined with less coverage at home and abroad,Teniposide (VM-26) with Oxaliplatin combined with the two drugs and Teniposide(VM-26), oxaliplatin and cisplatin combined with three reported less drug.The main purpose of this study:1.Two-drug(platinum Wilfordii with imatinib + L-OHP) Whether or not the application of United is stronger than single-drug(L-OHP) on the gastric cancer cells and synergy mechanisms.2.Up in the above-mentioned basic.three drugs(imatinib Wilfordii + platinum oxaliplatin,cisplatin) combined with strong double-Can(Platinum Wilfordii imatinib+L-OHP) combined with the destruction of the role of gastric cancer cells efficiency mechanisms.3 These results confirm at the trials,further defined the three drugs(imatinib Wilfordii+platinum oxaliplatin,cisplatin) when combined with the possibility of reduction of drug dosage and achieved efficiency results for future clinical work provide a theoretical basis.Material and methods:1.Human gastric cancer cell BGC-823 was chosen as the trial material.2.Chemotherapeutic drugs included VM-26,cisplatine(DDP),oxaliplatine(OXA).3.MTT assay was used to examine suppressive rate of cell growth dealt with various concentration of VM-26,DDP,OXA single and combined with the other drugs for 48 hour. 4.The development of cell cycle and apoptosis induced by different drugs was examined by flow cytometry at 0,12,24 and 48h in smaller concentration alone and in combination.5.The protein expression of cell apoptosis associated genes capase-9 and livin was examined by immunochemistry in the depent on management group.6.with SPSS10.0 software package,one-way ANOVA and chi-square test were used to analyze all experimental datum;rates was compared to each other byχ~2 test,size of the test was P＜0.05.Results:1.MTT assay showed that various concentration of OXA,OXA/VM-26, OXA/VM-26/DDP single could effectively inhibit the growth of cell line BGC-823,compared all of the management groups to control group,difference of OD value had statistical meaning(P＜0.05).The value of IC50 of OXA, OXA/VM-26,OXA/VM-26/DDP is 20.00μg/ml,3.38/1.51μg/ml,0.87/0.39/ 0.52μg/ml,respectively.The results show that,OXA,OXA/VM-26, OXA/VM-26/DDP drugs can effectively inhibit the BGC-823 gastric cancer cell growth,its inhibitory effect at the concentration range must exist in a dose-response relationship.Double-inhibitory effect than the inhibiting effect of monotherapy,and three pairs of drugs than the inhibitory effect of the inhibitory effects of drugs,and a deal has significant difference between groups(P＜0.05). At the same molar concentration,the inhibitory effect on gastric cancer cells to the weak by the strong for OXA/VM-26/DDP＞OXA/VM-26＞OXA.2.Immunohistochemistry results showed that,2.5μg/ml of OXA,OXA/VM-26, OXA/VM-26/DDP treatment of gastric cancer cells BGC-823 48h,the apoptosis-related gene caspase-9 positive rate of protein expression increased significantly,livin protein expression positive rate decreased significantly. Treatment group and control group and treatment group were statistically significant differences between(P＜0.05).。3.Flow cytometry results showed that three groups of cells after drug treatment flow charts are typical hypodiploid apoptotic peak.Monotherapy group(OXA) at 0,12,24,48 h the apoptosis rate was 3.80%,5.89%,13.52%,31.68%;two-drug group(OXA/VM-26) at 0,12,24,48 h the apoptosis rate was 3.90%,11.99%,38.25%,69.11%;three drug groups(OXA/VM-26/DDP) at 0,12,24 h the apoptosis rate was 3.73%,42.79%,85.25%(in 48h almost cells apoptosis,no statistics)4.Three groups of cells after drug treatment,at 0,12,24,48 h single-drug group, G2/M cells was 24.86%,17.89%,11.32%,3.76%;S cells is 29.32%,33.57%,38.92%,43.27%;two-drug group G2/M cells was 27.02%,21.53%,16.32%,2.06%;S cells was 30.42%,34.67%,39.81%,46.72%;three drug group G2/M cells was 29.02%,18.35%,7.15%,0.76%;S cells was 28.32%,39.74%,52.63%,65.86%.Each group compared with the 0h,apoptosis and cycle were statistically significant(P＜0.05).United three drug treatment in order to increase the rate of apoptosis,cell cycle distribution of the different groups.Conclusion:1.OXA,OXA/VM-26,OXA/VM-26/DDP gastric cancer cells can inhibit the growth of BGC-823,this inhibitory effect at a certain concentration range of dose-dependent manner.At the same molar concentration,the inhibitory effect on gastric cancer cells to the weak by the strong for OXA/VM-26/DDP＞OXA/VM-26＞OXA.2.OXA,OXA/VM-26,OXA/VM-26/DDP apoptosis-related genes may increase caspase-9 protein expression can be reduced Iivivin apoptosis suppressor gene protein expression,and this role OXA/VM-26/DDP＞OXA/VM-26＞OXA.Cell gene expression regulation are the three groups of drug-induced one of the mechanisms of apoptosis.3.Chemotherapy-induced apoptosis are the main anti-tumor cell mechanisms,the impact of cell cycle distribution and gene expression of apoptosis control and drug-induced apoptosis in the mechanism.Ability to induce apoptosis OXA/VM-26/DDP＞OXA/VM-26＞OXA,three groups of different cell cycle distribution. |
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