TP53INP1高表达在砷剂杀伤肺腺癌细胞中的增敏作用

Improving the expression of TP53INP1 in A549 cells enhances the sensitivity of cells to arsenic treatment

目的构建TP53INP1高表达的肺腺癌A549细胞,初步研究提高TP53INP1的表达能否提高砷剂对肺腺癌细胞的杀伤作用。方法构建TP53INP1重组真核表达质粒,以慢病毒为载体将其转染到A549细胞,建立稳定高表达TP53INP1基因的A549-TP53INP1细胞株,以流式细胞术和MTT实验检测As_2O_3处理后A549-TP53INP1细胞的凋亡和存活率。结果成功构建稳定A549-TP53INP1细胞株。流式细胞术结果显示,相同剂量As2O3作用下(5~40μmol/L),A549-TP53INP1细胞凋亡率[(15.6±3.5)%]显著高于A549细胞[(10.0±2.5)%](P<0.05)。MTT实验显示,As_2O_3处理后A549-TP53INP1细胞的IC50值[(44.64±6.84)μmol/L]显著低于A549细胞[(54.25±6.13)μmol/L](P<0.05)。结论 TP53INP1高表达可增加砷剂对肺腺癌细胞的杀灭作用,提示TP53INP1可作为砷剂治疗肺癌的增敏靶点。

Objective To explore if improving the expression of TP53INP1 could enhance the sensitivity of A549 cells to arsenic. Methods The eukaryotic express vector containing TP53INP1 gene was transferred into A549 cells by using lentivirus vector. Cell apoptosis and cell viability after arsenic treatment were assessed by flow cytometry and MTT assay, respectively. Results The protein expression level of TP53INP1 was increased in A549 cells transferred with eukaryotic express vector containing TP53INP1 gene,which led to an increase in apoptosis and a decrease in cell viability. Compared with A549 cells,significant increase in apoptosis was found in A549-TP53INP1 cells when treated with As_2O_3（ 5- 40 μmol/L）. In addiation,the IC50 of As_2O_3 in A549-TP53INP1（（ 44. 64 ± 6. 84） μmol/L） cells was significantly lower than that of the A549 group（（ 54. 25 ± 6. 13） μmol/L）（ P 0. 05）. Conclusion Enhancement of TP53INP1 can significantly improve apoptosis response and enhance sensitivity of A549 cells to arsenic. It is suggested that TP53INP1 could be used as a new target in arsenic-based cancer treatment.