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背景与目的:乏氧是恶性肿瘤中常见的现象。乏氧时肿瘤细胞对化疗抗拒,细胞凋亡减少。本实验通过研究乏氧对肺腺癌A549细胞(野生型P53)多药耐药蛋白表达及细胞凋亡的影响,探讨乏氧在多柔比星诱导细胞凋亡中的作用。方法:乏氧条件下(2%O2)人肺腺癌细胞株A549体外培养24 h,免疫组化法检测乏氧诱导因子-1α(H IF-1α)、P-糖蛋白(P-gp)和P53蛋白的表达;MTT法检测乏氧条件下A549细胞在多柔比星作用下的存活率;应用流式细胞仪检测细胞凋亡。结果:①乏氧条件下A549中H IF-1α、P-gp和P53蛋白的表达明显较正常氧浓度下增高,H IF-1α蛋白的表达与P-gp和P53蛋白的表达存在明显的相关性。②乏氧条件下A549细胞对多柔比星的耐药性明显增强,多柔比星诱导细胞凋亡率明显减低。结论:乏氧情况下,A549细胞能够通过H IF-1α上调P-gp和P53蛋白的表达;A549细胞在乏氧条件下多柔比星诱导细胞凋亡存在非P53依赖途径。
Background and Objective: Hypoxia is a common phenomenon in malignant tumors. Tumor cells in hypoxia resistant to chemotherapy, reduced apoptosis. In this study, we investigated the effect of hypoxia on multidrug resistance protein expression and apoptosis of lung adenocarcinoma A549 cells (wild-type P53) and the role of hypoxia in doxorubicin-induced apoptosis. METHODS: Human lung adenocarcinoma cell line A549 was cultured in vitro for 24 h under hypoxic conditions (2% O2). The expressions of HIF-1α, P-gp, And P53 protein. MTT assay was used to detect the survival rate of A549 cells treated with doxorubicin under hypoxia condition. Cell apoptosis was detected by flow cytometry. Results: ① The expression of HIF-1α, P-gp and P53 protein in A549 cells under hypoxia was significantly higher than that under normal oxygen concentration, and the expression of HIF-1α protein was significantly correlated with the expression of P-gp and P53 proteins Sex. ② Under hypoxic conditions, the resistance of A549 cells to doxorubicin was significantly enhanced, and the apoptosis rate induced by doxorubicin was significantly reduced. CONCLUSION: A549 cells can up-regulate the expression of P-gp and P53 protein by HIF-1α under hypoxic condition. There is a non-P53-dependent pathway in A549 cells induced by doxorubicin under hypoxia condition.