三氧化二砷体外对人EGFR T790M肺腺癌细胞抑制作用的研究

Antiproliferative effects and mechanism of As_2O_3 on EGFR T790M mutation in human non-small cell lung cancer cell line H1975

目的观察三氧化二砷对在体外对EGFR T790M突变非小细胞肺癌H1975细胞的生长抑制作用。方法运用MTT法检测三氧化二砷对H1975细胞增殖抑制,流式细胞仪检测细胞周期变化。倒置显微镜观察三氧化二砷作用下细胞形态变化。结果不同浓度的三氧化二砷在体外均能明显抑制H1975细胞的增殖,且具有时间和浓度依赖性,与浓度和时间呈正比。倒置显微镜观察发现三氧化二砷具有诱导H1975细胞出现核固缩、染色质凝集等凋亡形态改变。流式细胞仪检测提示细胞周期停留在G0/G1期。结论三氧化二砷在体外能抑制EGFRT790M突变肺癌细胞增殖、诱导调亡和改变细胞周期的作用。

OBJECTIVE To research the inhibitory effects and mechanism of As2O3 on acquired epidermal growth factor receptor tyrosine kinase inhibitors（EGFR TKIs） resistant in human non-small cell lung cancer cell line H1975 with EGFR T790M mutation in vitro.METHODS The inhibitory effects on H1975 cells exposed to As2O3 were evaluated by MTT method.The morphological changes of apoptosis induced by As2O3 were observed by inverted microscope.Cell cycle was detected by flow cytometry.RESULTS The MTT assay showed As2O3 had significantly antiproliferative effects with dose-dependent and time-dependent.Typical apoptotic morphologic changes were observed by inverted microscope,such as nuclear condensation and chromatin condensation.Flow cytometry assay showed that cell cycle was arrested at the G0/G1 phase on H1975 cells.CONCLUSION As2O3 can exert inhibitory effects on acquired EGFR TKIs resistant in human non-small cell lung cancer cell line H1975 with EGFR T790M mutation and it also can change the distribution of cell cycle and induce apoptosis.