Establishment Of 5-fluorouracil-multidrug-resistant Human Gastric Cancer Cell Line BGC823/5-FU And Study On Its Drug Resistant Mechanism And Reversal Of Mifepristone

Gastric cancer is one of the most common malignant tumors. As most of patients suffer from progressive cancer, chemical therapy plays an important role in combined therapy. 5-Fluorouracil (5-FU) is one of the most effective anticancer drugs used in the chemotherapy of gastric cancer. However, a significant number of tumors often fail to respond to chemotherapy, because tumors become resistant to 5-FU and several other anticancer drugs after consecutive treatments. Therefore, it is very important to understand mechanism of 5-FU resistance of gastric cancer and mifepristone reversing multidrug resistance of gastric cancer and find new resistance modifying agents (RMAs) for better treatment of tumors. The major research procedures and results are as follows:1. Establishment of 5-fluorouracil-multidrug-resistant cell lineBGC823/5-FU and its biological characteristicsTo investigate the mechanism of 5-FU resistance of gastric cancer, a 5-fluorouracil-resistant cell line from a Chinese gastric cancer was established by intermittent high dose 5-Fluorouracil, showed an over 500-fold increased resistant to 5-FU. BGC823/5-FU cells showed cross- resistant to VCR, VP-16 and HHT. Compared with its parent cells, the morphology was changed. Flow cytometry was used to detect the P - glycoprotein on the surface of the cells and the intracellular concentration of DNR, BGC823/5-FU over expressed P -glycoprotein and the intracellular DNR accumulation was decreased in BGC823/5-FU, suggesting that this subline was classically multidrug resistance and could be good experimental modal for study of multidrug resistance...