Study On Reversion Of Cisplatin Resistant In Ovarian Cancer Cell Lines SKOV3/DDP And Reversal Mechanisms

Objective: The morbidity of ovarian malignant tumor is rank of the third in female genital malignant tumor, but the first mortality.The five-year-survival is nearly 20%-30% The cytoreductive surgery and multiply course of treatment is the basic treatment principle at present. Chemotherapy plays a very important role. But the tumor cells can show drug resistance which influences the curative effect and lead to the failure of chemotherapy and tumor recurrence. How to overcome the multi-drug resistance has become an important problem for the chemotherapy curative effect. It is also concerned by scientists home and abroad. Recent studies show that .neutral glycosphingolipids which is the main component of cell membrane is concerned with tumor multi-drug resistance. Some scientists get the idea whether it is possible to reverse the tumor multi-drug resistance by inhibition of neutral glycosphingolipids from synthesis. This mechanism is possible to become a new way to reverse the tumor multi-drug resistance. To make a further study on the relationship of neutral glycosphingolipids and tumor multi-drug resistance, the expression rule of neutral glycosphingolipids in ovarian cancer SKOV3 cells and its drug resistance lines-SKOV3/DDP cells are studied. The effect of normal and abnormal expression ofneutral glycosphingolipids on reversion of drug resistance is analyzed and the result shows that there is a connection between the change of content of neutral glycosphingolipids and drug resistance.Scientists abroad find that TAM, mainly used in the therapy of breast cancer, and RU486, mainly used in terminating pregnancy, show some effect on the therapy of drug resistant ovarian cancer. The mechanism may be relevant to P-glucoprotien, MRP, glycosylceramide.This study fixed eyes upon the research of the reversion of drug resistant ovarian cancer by TAM, RU486, which will be able to offer a powerful scientific basis for theexploration of the mechanism of reversion of drug resistance and the clinical therapy of drug resistant ovarian cancer patient.Methods: Ovarian cancer cell line SKOV3 and its drug resistant cell line SKOV3/DDP is cultured in vitro and collected. The reversion effects of TAM, RU486 on MDR in SKOV3/DDP was determined by MTT (thiazolyl blue) method. N-GSL (neutral glycosphingolipids) of the cells is isolated and purified with the modified Hakamori's method. Changes of CMH content are analyzed by HPTLC (high performance thin layer chromatography).Results: (1) TAM and RU486 can reverse the drug resistance of SKOV3/DDP cells and increase the sensitivity of SKOV3/DDP cells to DDP; (2) The content of CMH in SKOV3/DDP cells are significantly higher than it in SKOV3 cells; (3) The content of CMH in SKOV3/DDP decreased and is near to the content of it in SKOV3 cells after treated by TAM and RU486.Conclusion: TAM and RU486 can reverse DDP resistance human ovarian cancer cell lines. TAM and RU486 can change the content of neutral glycosphingolipids in SKOV3/DDP cells. The control of neutral glycosphingolipids expression is relevant to tumor cells drug resistance.