인체 폐암세포주에서 다약제내성유전자 표현과 Buthionine Sulfoximine 투여가 Cisplatin 및 Adriamycin 의 세포독성도에 미치는 영향

Objectives: Cisplatin and adriamycin have been proven to be the most effective drugs for lung cancer, However, repeated courses of chemotherapy frequently result in a decreased therapeutic response because of the emergence of an acquired drug-resistance. Recently it has been demonstrated that the resistance to cisplatin, adriamycin or alkylating agents may be due to elevated intracellular glutathione levels in human and rodent tumor cell lines. This study was aimed to investigate any relationship between intracellular glutathione levels and sensitivity to cisplatin and adriamycin, and whether cytotoxicity to cisplatin and adriamycin could be in- creased with buthionine sulfoximine. Methods: We used human SCLC cell line, NCI-H209, and three human NSCLC cell lines, NCI-H727, NCI- H810 and NCI-H1299. The multidrug resistance gene expression was investigated by RNA slot blot analysis. The intracellular glutathione levels was examined before and after administration of buthionine sulfoximine. Drug sensitivity assays were performed using a modified MTT method. Results: 1) The resistance to adriamycin and cisplatin in human lung cancer ce11 lines was closely related to MDR1 expression level rather than that of intracellular glutathione level. Cisplatin resistance seemed to be related to the glutathione level above some concentrations. 2) 5-Fluorouracil resistance seemed not to be related to MDR1 expression or glutathione level. 3) Buthionine sulfoximine was not effective on adriamycin and cisplatin cytotoxicity in MDR1 positive cells, but effective in MDR1 negative cells. Conclusion: It is suggested that buthionine sulfoximine is an effective supplement to adriamycin and cisplatin in MDR1 negative cells. And its effectiveness in human lung cancer patients needs a further clinical studies.