Mcl-1参与非小细胞肺癌对吉非替尼耐药的实验研究

目的:探究人髓细胞白血病基因-1(myeloid cell leukemia-1,Mcl-1)是否参与非小细胞肺癌对吉非替尼的耐药。方法:应用Western blot检测Mcl-1在吉非替尼敏感细胞PC-9和耐药细胞H1975表达差异;梯度浓度的吉非替尼作用于PC-9细胞后,Western blot实验检测B淋巴细胞瘤-2基因(B-cell lymphoma-2,Bcl-2)家族中抗凋亡蛋白的表达变化;应用Western blot实验检测Mcl-1在PC-9和H1975细胞内降解速度差异。结果:Mcl-1在PC-9细胞内的表达明显低于H1975细胞,差异有统计学意义(P0.05),并且随着吉非替尼作用浓度的升高,Mcl-1表达逐渐降低,而Bcl-2和Bcl-x L表达基本不变,并且PC-9细胞内Mcl-1降解更迅速,半衰期明显缩短。结论:非小细胞肺癌对吉非替尼耐药可能与Mcl-1的表达量上调,降解速度减慢,半衰期延长有关。

Mcl-1 was involved in the Drug Resistance of Gefitinib in the Non-small Cell Lung Cancer

ABSTRACT Objective: Explore whether Mcl-1 (myeloid cell leukemia-1) participates in gefitinib resistance of non-small cell lung cancer. Methods: Western blot was used to test Mcl-1 expression in gefitinib sensitive cell PC-9 and resistant cell H1975; PC-9 cell was treated by gradient concentration of gefitinib, then western blot was used to test antiapoptotic proteins expressions of the Bcl - 2(B-cell lymphoma-2) family and Mcl-1 degradation speed in PC -9 cell and H1975 cell. Results: The expression of Mcl-1 in PC-9 was signifi- cantly lower than that in the H1975 cell(P<0.05), and the expression of Mcl - 1 gradually reduced along with the increase of gefitinib con- centration, while the expression of Bcl - 2 and Bcl - xl showed no signiifcant change, and Mcl-1 was degraded more quickly in PC-9 cell than in H1975 cell. Conclusion: Up-regulated expression, slow degradation and the half-life extension of mcl-1 may contribute to the gefitinib resistance of non-small cell lung cancer.