不同用药顺序吉非替尼、多西他赛联用对非小细胞肺癌细胞的体外抑制作用

Sequence-dependent antiproliferative effects of gefitinib combined with docetaxel in non-small cell lung cancer cells in vitro

目的探讨不同用药顺序吉非替尼、多西他赛(DXT)联用对非小细胞肺癌(NSCLC)细胞的体外抑制作用。方法选择人肺癌细胞株PC-9、PC-9/G、A549,用MTT法、流式细胞技术分别检测不同顺序吉非替尼、DXT联用对3种细胞存活率、周期及凋亡的影响;用药顺序分先用DXT、后用吉非替尼(D→G组)及先用吉非替尼、后用DXT组(G→D组)。结果与G→D组比较,D→G组细胞存活率显著减少,可使细胞阻滞在G2～M期,并增强DXT诱导的细胞凋亡(P均<0.05);G→D组可使细胞阻滞在G0～G1期,并减少DXT诱导的细胞凋亡。结论先用DXT、后用吉非替尼为抑制NSCLC细胞增殖的最佳联用方案。

Objective To explore the sequence-dependent antiproliferative effects of gefitinib combined with docetaxel in non-small cell lung cancer cells in vitro. Methods PC-9, PC-9/G and A549 cell lines were chosed. The cell survival rates were measured by MTT assay, cell cycle distribution and apoptosis were measured by flow cytometry docetaxel. Ac- cording to the sequence of administration of gefitinib combined with docetaxel, the cells were divided into docetaxe followed by gefitinib group （ D→G group） and gefitinib followed by docetaxel group （ G→D group）. Results Compared with the G →D group, D→G group remarkably decreased cell survival, induced G2-M phase arrest and enhanced apoptosis induced by docetaxel; in contrast, G→D group induced G0-G1 phase arrest and decreased apoptosis induced by doeetaxel. Conclusion Sequential administration of docetaxel followed by gefitinib is optimal combination schedule for the antiproliferative effects of non-small cell lung cancer cells.