Inhibition Effect Of Fluorouracil Combined With Anthocyanin To Gastric Cancer Cell In Vitro

Background:Anthocyanins are rude and water soluable, which are widely exist in various of plants. They are important anti-oxidant pigments. Anthocyanins also have effects of eliminating ROS. They can also improve the side-effect of chemotherapy and have an important protective effect to the normal tissue. Also, anthocyanins have already been proven of apoptosis tumor cells. However, in the chemotherapy process of tumor cells in vitro with various chemotherapy agents, anthocyanina are proven of anti-oxidant effect to protect the tumor cells at the same time of apoptosis effect, which has an antagonism effect to the latter. The mechanism is related with Nrf2-Keapl-ARE pathway, which mainly concern to the shift of Nrf2and the up-regulation of a serious of downstream oxidative genes. This effect may affect the future use of anthocyanins in clinic.Objective:To investigate the effect to cell growth for gastric cancer cell sgc-7901when been treated by cyanidin-3-glucopyranoside(C3G) and fluorouracil, and approach the possible mechanism. Methods:MTT assay was used to determine the cell survival rates of both single and double drugs, calculate IC50to draw the Isobologram. Determine the synergism or antagonism effect by the Isobologram. The expression of Nrf2, Keap1and their downstream antioxidant genes (HO-1and NQO1) were determined by realtime quantitative PCR, changes of ROS in each group were determined by Flow CytoMeter.Results:With single drug used we found IC505-FU=15.752uM,IC50C3G=1.765ug/ml. With double drugs of fixed5-FU and changing C3G we found the results of IC505-fU=2=1.71ug/ml, IC505-FU=5=1.616ug/ml, IC505-FU=8=1.444ug/ml IC505-FU=10=1.172ug/ml, all points were above the Isobologram. Realtime quantitative PCR demonstrated that C3G up-regulated the expression of anti-oxidative genes as HO-1and NQO1(p<0.05), the expressions of the up-stream Nrf2and Keap1showed no obvious change. Flow CytoMeter demonstrate ROS negatively related to the cell survival rates.Conclusion:5-FU combined with C3G showed some addictive effect on gastric tumor cells SGC-7901in vitro, but it is mostly antagonism effect, without obvious synergism. The mechanism is probably related to the up-regulation of anti-oxidative genes in tumor cells.