黄连素抑制肺腺癌核转录因子-κB活性的影响及其与顺铂耐药关系研究

Effect of berberine on the reversing cisplatin-resistant of lung adenocarcinoma cell by inhibiting nuclear factor-κB activity

目的：观察黄连素对肺癌细胞中顺铂细胞毒性的影响并探讨其机制。方法：选用肺癌顺铂（CDDP）耐药细胞株A549/CDDP,四甲基偶氮唑蓝法测定药物对细胞存活率的影响,蛋白免疫印记法测定IκBα、p65的表达水平。并用p65 siRNA转染A549/CDDP细胞沉默p65的表达,而降低核转录因子（NF）-κB的活性。结果：CDDP耐药肺癌细胞A549/CDDP与敏感细胞A549相比,p65的表达水平显著升高,而IκBα的表达水平显著降低,p65 siRNA沉默A549/CDDP细胞p65的表达降低NF-κB的活性后能显著逆转CDDP耐药（P〈0.01）;20μmol/L的黄连素能显著增加A549/CDDP细胞对CDDP的敏感性,且5~20μmol/L的黄连素能浓度依赖性地降低A549/CDDP细胞中p65的表达,但增加IκBα的表达（P〈0.01）。结论：黄连素通过抑制NF-κB的活性逆转肺腺癌细胞中CDDP耐药。

Objective： To observe the effects of berberine on the toxicity of CDDP,and its mechanism. Methods： The cell survival rate,and expressions of IκBα and p65 in CDDP-resistant A549 cell line（ A549 / CDDP） were measured by MTT assay and westen blotting,respectively. The expression of p65 was silenced by p65 siRNA transfecting the A549 / CDDP cells,which was used to decrease the NF-κB activity. Results： Compared with the CDDP sensitive cells（ A549 cells）,the expressions of p65 and IκBα increased and decreased significantly in A549 / CDDP cells,respectively（ P〈0. 01）. The activity of NF-κB was decreased by the p65 siRNA silencing the expression of p65 in A549 / CDDP cells,which could reversed the CDDP resistance（ P〈0. 01）. The 20 μmol / L berberine could obviously enhance the sensitivity of A549 / CDDP cells to CDDP,and 5 to 20 μmol / L berberine could decreased the expression of p65 in a dose-dependent manner,while the expression of IκBα was obviously enhanced by berberine（ P〈0. 01）. Conclusions： Berberine can reverse the resistance of A549 lung adenocarcinoma cells to cisplatin by inhibiting NF-κB.