乏氧对肺腺癌A549细胞P糖蛋白和多药耐药相关蛋白表达的影响

目的 通过研究乏氧对人肺腺癌细胞株A549的P糖蛋白(P-gp)和多药耐药相关蛋白(MRP)表达的影响,探讨乏氧在引起肿瘤细胞多药耐药中的作用。方法 乏氧条件下(2％O2)人肺腺癌细胞株A549体外培养24h,丙酮固定后运用免疫组织化学的方法对乏氧诱导因子-1α(HIE-1α)、P-gp和MRP的表达进行检测,并用MTT法检测乏氧条件下A549细胞在阿霉素和顺铂作用下的存活率。结果 乏氧条件下人肺腺癌细胞株A549中乏氧诱导因子-1α、P-糖蛋白和多药耐药相关蛋白的表达明显较正常氧浓度下增高,HIF-1α与P-gp、MRP的表达增高存在明显的相关性。乏氧条件下人肺腺癌细胞株A549对阿霉素的耐药性明显增强。结论 在人肺腺癌A549细胞中HIF-1α蛋白表达与P-gp和MRP表达存在明显的相关性。

Effects of hypoxia on expression of P-glycoprotein and multidrug resistance protein in human lung adenocarcinoma A549 cell line

OBJECTIVE: To study the effects of hypoxia on expression of P-gp and multidrug resistance protein in human lung adenocarcinoma A549 cell line, and to explore the probable mechanism of hypoxia in tumor cell of MDR. METHODS: Culturing human lung adenocarcinoma A549 cell in hypoxia (2%O2) for 24 h, the expression of hypoxia inducible factor-1alpha, P-gp and multidrug resistance protein was detected by using immunohistochemistry, and after action of adriamycin or cisplatin in hypoxia (2%O2) for 24, the cell survival rate was detected by MTT. RESULTS: The expression of hypoxia inducible factor-1alpha, P-gp and multidrug resistance protein in hypoxia were higher than the expression in anoxia, and correlation between the expression of HIF-1alpha and P-gp or multidrug resistance protein was observed (P < 0.05). The resistance of adriamycin of A549 cell was enhanced in hypoxia. CONCLUSION: The resistance of tumor chemotherapy is enhanced in hypoxia. The expression of HIF-1alpha is obviously correlated with the expression of P-gp and MRP in A549 cell.