Effects Of2-deoxy-D-glucose And Oxaliplatin On The Proliferation And Apoptosis Of Human Hepatoma Cell Line SMMC-7721

Background and purpose:Liver cancer is a common digestive tumors.According to statistics, the incidence rate of liver cancer is nearly0.2%o in China, second only to stomach cancer.Liver cancer is a serious threat to people’s physical and mental health.Chemotherapy as an important part of comprehensive treatment of liver cancer its current clinical effect is far short of expectations. This is not only chemotherapy drugs has greater toxicity and not very effective, but also tumor cells susceptible to existing chemotherapy drug-induced resistance.Based on such current search, the development of new chemotherapy treatment of liver cancer has become a research hotspot.The warburg effect was first discovered and proposed by the German biochemist Otto Heinrich Warburg.The effect pointed out that the tumor cells even in the aerobic environment would be more inclined to use anaerobic glycolysis metabolic pathways to obtain the energy of their own need.This is different from the metabolic characteristics of normal cells that obtain the energy primarily through aerobic metabolism.This effect allows us not only new understanding of the metabolic characteristics of tumor cells, at the same time,it is open the idea of that we can take advantage of the metabolic characteristics of tumor cells to take glycolysis therapy.If we apply the glycolytic inhibitor treatment to cancer, drugs in the treatment process will inhibit the growth of tumor cells with minimal impact on normal cells.This is exactly an ideal treatment what we are pursuing.As a glycolytic inhibitor,the therapeutic potential of2-deoxy-D-glucose (2-DG) on the tumor is gradually get people’s attention. Previous studies have shown that2-DG on pancreatic cancer,breast cancer has a better inhibition of the growth and proliferation. While as a adjuvant of radiotherapy2-DG can improve the sensitivity to radiotherapy.Oxaliplatin is a third generation platinum chemotherapy drugs and the first-line clinical chemotherapy drugs now. Studies have shown that oxaliplatin can produce hydration derivatives acting on the tumor cell DNA, the formation of cross-linking between the chain and chain, thereby inhibiting DNA synthesis, resulting in anti-tumor activity. Oxaliplatin has not only been used for the treatment of colorectal cancer, and clinical application for liver cancer has a better therapeutic effect.From now on the inhibitory effect of2-DG on liver cancer cells as well as its ability to improve the efficacy of oxaliplatin when they combined has also not been reported in the literature.In this study,we want to find the inhibitory effect on liver cancer cells which was be treated by2-DG and oxaliplatin alone or both from the perspective of in vitro cytology. We also have explored the mechanism of2-DG. With a view to provide a new treatment ideas and experimental evidence for the clinical treatment of liver cancer.Methods:1. Human hepatic carcinoma cell SMMC-7721was supplied by the central experiment of He Nan cancer hospital.Cultivate the cells with the DMEM complete culture media containing10%fetal bovine serum in the37℃,5%CO2saturated humidity incubator.2. MTT test was used to estimate the inhibition of proliferation on SMMC-7721. 3. Apoptosis rate and cell cycle were assayed by flow cytometry.4. Analyzed the activity of caspase3by fluorescence intensity.Results:1.2-DG and L-OHP at different concentrations could inhibit the growth of SMMC-7721cell lines obviously.Growth inhibition of SMMC-7721cell strongly depended on the concentration and the treatment time of2-DG or L-OHP.When they worked combinedly,the effect was additive.2.2-DG induced cell apoptosis and arrested cell at G2/M phase.When combined with L-OHP,two drugs induced more severe apoptosis and arrested cell at S and G2/M phase.3. The activity of caspase3increased when the two drugs used together.Conclusion:2-DG can inhibit the growth of hepatoma cell line SMMC-7721.When it combined with L-OHP,it can improve the ability of L-OHP to attack the tumor cell.The mechanism might be related to the effect on elevation of caspase3activity.