摘要目的 探讨抑制nm23-H1基因的表达后,紫杉醇脂质体对人肺腺癌A549细胞化疗敏感性的影响.方法 以人肺腺癌A549细胞为研究对象,将其分为nm23-H1-小干扰RNA(siRNA)转染组和未转染组.采用Western blot法检测两组A549细胞中nm23-H1蛋白的表达情况,采用四甲基偶氮唑蓝(MTT)法检测紫杉醇脂质体对两组A549细胞的生长抑制率,以流式细胞仪检测A549细胞的凋亡和细胞周期的变化.结果 转染nm23-H1-siRNA后,A549细胞中nm23-H1蛋白的表达水平明显降低.紫杉醇脂质体作用48 h后,A549细胞的生长抑制率随药物浓度的升高而升高,且转染组细胞的抑制率更高.当紫杉醇脂质体浓度≥5 μg/ml时,转染组的抑制效率明显高于未转染组(均P＜0.05).转染nm23-H1-siRNA后,A549细胞的凋亡率[(65.62±4.36)%]较未转染组明显增加[(43.78±5.56)%,P＜0.05],S期和G2/M期细胞所占的比例则有所下降[S期:分别为(15.73±3.21)%和(25.56±4.01)%,P＜0.05;G2/M期:分别为(31.91±3.12)%和(39.41±4.21)%,P＜0.05].结论 nm23-H1基因与紫杉醇脂质体的化疗抵抗有关,抑制nm23-H1基因的表达可以增强紫杉醇脂质体的化疗敏感性.

abstractsObjective To study the chemosensitivity of lung adenocarcinoma cell line A549 cells to liposome-encapsulated paclitaxel after treatment by nm23-H1-small interference RNA (nm23-H1-siRNA) in vitro. Methods The A549 cells were divided into two groups: non-transfected group and nm23-H1-siRNA-transfected group. Western blot analysis was used to detect the expression of nm23-H1. MTT and flow cytometry were used to determine the cell mortality rate, apoptosis rate and cell cycle after liposome-encapsulated paclitaxel treatment in both groups. Results The expression of nm23-H1 in A549 cells was significantly decreased after transfection with nm23-H1-siRNA. After treatment for 48 hours with liposome-encapsulated paclitaxel, the cell mortality rate was increased with the increasing concentration of liposome-encapsulated paclitaxel in both groups, but increased higher in the nm23-H1-siRNA-transfected group. When the concentration of liposome-encapsulated paclitaxel was above 5 μg/ml, the cell mortality rate was significantly higher than that in the non-transfected group (P<0.05). The proportion of apoptotic cells also increased in the nm23-H1-siRNA-transfected group, compared with that of the non-transfected group (t=3.812,P<0.05), while the proportion of cells at S and G2/M phase decreased after transfection with nm23-H1-siRNA (S phase:t=8.356,P<0.05;G2/M phase:t=7.256,P<0.05). Conclusions Nm23-H1 is related with the chemoresistance to liposome-encapsulated paclitaxel in lung adenocarcinoma cell line A549 cells. Inhibition of the expression of nm23-H1 by nm23-H1-siRNA can improve the in vitro chemosensitivity of A549 cells to liposome-encapsulated paclitaxel.