化疗药物杀伤原代胃癌细胞效应与P-糖蛋白和GST-π表达的关系
摘要
BACKGROUND & OBJECTIVE: Drug-resistance is a major factor of influencing treatment efficacy of advanced gastric cancer. This study was to evaluate in vitro antitumor effects of different chemotherapeutic drugs on fresh human gastric cancer cells, and explore their relationships with expressions of P-glycoprotein (P-gp), and glutathione S transferase-π (GST-π) in human gastric cancer tissue. METHODS: A total of 39 specimens of highly purified gastric cancer cells were separately exposed to 5-fluorouracil (5-FU), cisplatin (DDP), mitomycin C (MMC), adriamycin (ADM), and hydroxycamptothecin (HCPT). Inhibitory rate of cells was detected by MU assay. Metabolic activity of cells was detected by trypan blue exclusive assay. Cell apoptosis was detected by in situ terminal deoxynucleotidyl transferase assay (TdT assay). Expressions of GST-π and P-gp in gastric cancer tissues were detected by immunohistochemistry. RESULTS: After exposure to antitumor drugs, morphologic changes, decrease of metabolic activity, and apoptosis were appeared in gastric cancer cells. Inhibitory rates of cancer cells exposed to MMC, DDP, 5-FU were significantly higher than those of cells exposed to ADM, and HCPT [(38.6±7.7)%, (38.1±8.8)%, and (37.8±10.3)%vs. (31.9±10.4)%, and (29.7±10.2)%, P＜0.01. Apoptosis rate of cancer cells exposed to CDDP, 5-FU, and MMC were significantly higher than those of cells exposed to HCPT, and ADM [(32.1±7.7)%, (31.1±8.8)%, and (29.8±6.3)% vs. (21.9±7.4)%, and (19.9±7.4)%, P＜0.05]. Positive rate of GST-π was 66.7% (26/39), that of P-gp was 59.0%(23/39). GST-π positive cells showed resistance to DDP and MMC, P-gp positive cells showed resistance to ADM and HCPT. CONCLUSIONS: Overexpressions of P-gp and GST-π might contribute to drug-resistance of tumor. Detection of GST-π and P-gp, together with MTT chemosensitivity test, might be useful for selecting more effective chemotherapeutic drugs.