| Objective: Cisplatin (Cisplatin, DDP) is a highly effective andbroad-Spectrum anti-cancer drugs, and has been widely used in the treatmentof various tumors,the treatment effect is dose-related, However, large dose ofDDP can cause irreversible renal damage and serious gastrointestinal reactions,Therefore, to some extent, the adverse reactions limit its clinical application.Nedaplatin (nedaplatin, NDP) is the2nd generation platinum compound, andthe anti-tumor mechanism is similiar to cisplatin, but the renal toxicity andgastrointestinal adverse reactions are less than DDP, NDP is no need tohydrate, easy to use, and has no cross-resistance contrast with cisplatin,carboplatin. NDP in the clinical application of the head and neck cancer, smallcell lung cancer, non-small cell lung cancer, esophageal cancer and other solidtumors has been proven,a result of Japanese phase II clinical trial in the gastriccancer study is invalid, but yet to be a large-scale clinical trials to confirm.Another experimental results of chemotherapy drug by the MTT assay onhuman gastric cancer cell line (SGC-7901) Inhibition display, NDP hassignificant inhibitory effect on human gastric cancer cells, the maximalinhibition rate of is up to100%, and lower concentration has been inhibited,the results suggest that NDP on the effect of gastric cancer may be moreefficient than DDP. For this reason, this study will be through animalexperiments by different doses of NDP and DDP in nude mice with MGC-803gastric cancer xenografts to observe the change of diets, activities, bodyweights and tumor weights, to comprehensively analysis the antitumor effectsand influencing factors in transplanted gastric cancer MGC-803by NDP. onthis basis, the use of Flow cytometry technology to explore the gastric cancerMGC-803cell cycle of NDP, while using Western blot and RT-PCR todetect tumor p53mRNA and protein expression changes in order to investigate the effect of NDP on the treatment of gastric cancer, and toprovide new ideas and theoretical basis to guide the choice of chemotherapeu-tic drugs.Method:1,Nude mice model and experimental groups: the40Nudemouse injected by gastric cancer MGC-803tumor cells,and were randomlydivided into four chemotherapy group and a control group (n=8). DDPnude mice application total dose is1.5mg/kg, The three NDP nude miceapplication total dose are1.0mg/kg,2.0mg/kg,3.0mg/kg,and the controlgroup received the same volume of normal saline to simulate the clinical drugby intraperitoneal injection.2,Observe the General conditions in nude mouse:daily observed and recorded diets, toilets, activities and weight changes oftumor-bearing nude mouse, while observing adverse drug reactions.3,Explore the impact of gastric cancer MGC-803cell cycle from the use ofnedaplatin using flow cytometry technology. p53mRNA and proteinexpression changes of tumor tissue was detected by Western blot, RT-PCR,to analyze difference of different doses of NDP Group,DDP group and salinegroup.4,Statistical analysis: SPSS13.0software for statistical analysis ofeach set of data. Measurement data to X±s, multiple sets of samples werecompared using analysis of variance, P <0.05was considered statisticallysignificant.Results:1,Weight change of nude mouse bearing human tumor andinhibition rates: Body weights in different doses of NDP group and DDPgroup were significantly lower than the saline group (P <0.05); Tumorweights of chemotherapy groups were significantly lower than the controlgroup (P <0.05); the inhibition rates of low, medium and high dose group andDDP group were15.67%,26.87%,37.31%,47.01%.2,Flow cytometry cellcycle results: Results of Cell cycle shows, compared with saline controlgroup, that s-phase ratio of DDP chemotherapy was higher, and G0/G1, G2/Mcell ratio lower (P<0.05)；and in different dose group of NDP chemotherapy,G0/G1cells reduced, and s-phase cell ratio increased. s-phase cell ratios ofLow, medium and high dose in NDP group, lower than DDP group, but G0/G1 cell ratios were higher. Comparison between three NDP Groups, s-phase cellratio increased as the dose increased gradually.3,The P53mRNA results byRT-PCR: The P53gene expression levels of the chemotherapy groups weresignificantly higher than that the saline control group (P <0.05); in the threeNDP groups, p53gene expression levels showed dose-effect relationship,and with the drug dose increased, expression levels of p53mRNA wereincreased, but lower than the DDP group (P <0.05).4,detection of P53protin results by western blot:The P53protein expression levels of allchemotherapy groups were significantly higher than that of the saline controlgroup (P <0.05);in the three NDP groups, p53protein expression levelswere dose-effect relationship, and as the dose increased, the expression levelswere increased, but all lower than the DDP group (P <0.05), in which thehigh dose of the NDP group was close to the DDP group.Conclusion:1,The NDP groups acting on the gastric cancer MGC-803xenografts in nude mice, could inhibit tumor growth and displayed dose-effectrelationship, and were statistically significant, which the NDP group ofhigh-dose treatment was close to the DDP group.2,The different doses ofNDP Group increased the distribution of proliferating cells in S phase,blocking the DNA synthesis of cells in S phase, and could not enter the G2/M phase with affecting the normal operation of the cell cycle, and slowingdown cell growth.3,NDP and DDP chemotherapy enhanced the P53mRNAand protein expression in the nude mouse MGC-803gastric cancerxenografts, different doses of nedaplatin groups showed dose-responserelationship,and the expression level of high-dose NDP group was close tothe cisplatin group (P <0.05). |
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