Regulation Of The Expression Of N-GSLs And The Mechanisms Of Immune Escape In The Reversion Of MDR In Ovarian Cancer Cells(COC1/DDP And SKOV₃/Adr)

Objectives: The study was aimed to evaluate the relationship between MDR of ovarian cancer and expression of neutral glycosphingolipids in ovarian carcinoma cell lines, and to find out the change of immune antigen after occurance of MDR. This will be helpful to investigate the mechanism of MDR in ovarian carcinoma and search some new agents in the reversion of MDR and alternative treatment by immunotherapy . Methods: The effects of TAM and VRP (which have been shown to reverse MDR) on the growth of COCI/DDP and SKOV3/Adr were assayed by MTT method. N- GSLs of the cells were isolated and purified with the modified Hakamori?s method and analysised by HPTLC. Flow cytometry was used to detect the expression of HLA-l, HLA-2, B7-l, B7-2 in parent cell lines (COC1 and SKOV3 ) and multidrug resistant cell sublines (COCI/DDP and SKOV3/Adr). Results: The expression of N-GSLs was different between parent cell lines and resistant cell sublines, the level of CMII-I was higher in COC1/DDP and SKOV3/Adr than that in COC1 and SKOV3. TAM and VRP(l i g /ml) could partly reverse MDR of COC1IDDP and SKOV3/Adr, and 5 ii g /ml TAM and VRP could completely reverse it and render multidrug-resistant cells sensitive to chemotherapy, while the level of CMH concomitantly had shown a sharply decreased. Most kinds of tumor cells expressed MI-IC class I molecules, a minority also expressed HLA-2, B7- 1 and B7-2 molecules. However, the expression of cost imulator B7-l and B7-2 was higher in COC1/DDP and SKOV3/Adr than in COC1 and SKOV3. Conclusion: The expression of N-GSLs is associated with MDR, and CMH may be a kind of MDR related glycolipids. TAM and VRP can reverse MDR via inhibiting the synthesis of CMH, suggesting that this mechanism of action is a common denominator in chemosensitizing process. Tumor cells are easy to escape from the host immune surveillance. Compared withtheir parental sensitive cell lines, MDR cell sublines may be more easilyactivate the host T cell immune reaction. Adoptive cellular immunotherapyis a potential choice in the treatment of MDR cancers.