CAJ | 학술논문

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。
목적：연구동원이형합기인HOXA5적변화대소세포폐암다약내약성적영향，병탐토기작용궤제，평개기작위소세포폐암림상치료파점적가능성。방법실시형광정량PCR화면역인적법검측소세포폐암세포H69화다약내약세포주H69AR중HOXA5 mRNA화단백수평，채용표체질립화siRNA승고혹강저HOXA5기인표체수평，CCK8법분석세포대소세포폐암상용화료약물순박（Cisplatin，DDP）화족협을대（Etoposide，VP-16）민감성적변화。결과 H69세포중HOXA5 mRNA수평시내약세포주H69AR중적8.99배。HOXA5 siRNA현저강저H69세포중HOXA5적표체수평，강저료H69세포대DDP화VP-16적민감성。장HOXA5표체질립은정전염입H69AR세포，건립은정전염세포주，세포대DDP화VP-16민감성증가。결론 HOXA5가능삼여료소세포폐암내약과정，가능회성위소세포폐암림상치료적신파점。
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.