目的：研究同源异型盒基因HOXA5的变化对小细胞肺癌多药耐药性的影响，并探讨其作用机制，评价其作为小细胞肺癌临床治疗靶点的可能性。方法实时荧光定量PCR和免疫印迹法检测小细胞肺癌细胞H69和多药耐药细胞株H69AR中HOXA5 mRNA和蛋白水平，采用表达质粒和siRNA升高或降低HOXA5基因表达水平，CCK8法分析细胞对小细胞肺癌常用化疗药物顺铂（Cisplatin，DDP）和足叶乙甙（Etoposide，VP-16）敏感性的变化。结果 H69细胞中HOXA5 mRNA水平是耐药细胞株H69AR中的8.99倍。HOXA5 siRNA显著降低H69细胞中HOXA5的表达水平，降低了H69细胞对DDP和VP-16的敏感性。将HOXA5表达质粒稳定转染入H69AR细胞，建立稳定转染细胞株，细胞对DDP和VP-16敏感性增加。结论 HOXA5可能参与了小细胞肺癌耐药过程，可能会成为小细胞肺癌临床治疗的新靶点。%Objective To investigate the role of homeobox gene A5 (HOXA5) in multidrug resistance of human small cell lung cancer (SCLC) cells and the possibility of using HOXA5 as the therapeutic targets for SCLC treatment. Methods We examined HOXA5 mRNA and protein expressions in chemosensitive human SCLC cells (H69) and the multidrug-resistant SCLC cells (H69AR) using quantitative real-time PCR and immunoblotting. HOXA5 expression was then enhanced or suppressed by transfection of the cells with HOXA5 expression plasmids or small interference RNA (siRNA), and the chemosensitivity of transfected cells to cisplatin (DDP) and etoposide (VP-16) was evaluated using cell counting kit-8 (CCK8) assay. Results H69 cells showed a 8.99-fold higher expression of HOXA5 than H69AR cells. HOXA5 knockdown caused obvious reductions in the chemosensitivity of H69 cells to DDP and VP-16 with increased cells in G0/G1 phase; conversely, HOXA5 enhancement resulted in an increased sensitivity of H69AR cells to DDP and VP-16. Conclusion HOXA5 may play an important role in multidrug resistance of SCLC and can be a potential therapeutic target in clinical treatment of SCLC.
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