吉非替尼与多西他赛对不同肿瘤细胞株相互作用的实验研究

Effects of combination of gefitinib and docetaxel on various tumor cell lines in vitro

目的探讨吉非替尼与多西他赛以不同顺序同步或序贯给药对于不同细胞株的细胞增殖能力及细胞周期和凋亡的影响。方法用四甲基偶氮唑盐法检测同步、不同序贯疗法（多西他赛序贯吉非替尼或吉非替尼序贯多西他赛）对于A431、A549、SPC—A1及NCI—H292细胞株的细胞存活率的影响，并通过流式细胞仪检测不同的给药顺序下A549及A431细胞周期及凋亡的变化。结果两药联合采用不同的给药方式、在不同细胞株中表现出的作用不同：多西他赛序贯吉非替尼组对比单药组对细胞生长抑制作用在4种细胞株中均有增强；同步组及吉非替尼序贯多西他赛组对比单药组对细胞生长抑制作用在A549、SPC—A1、NCI—H292细胞株中均有减弱，表现出拮抗作用，而在A431细胞株中有所增强，表现为协同作用；设置一定的给药间期可削弱这种拮抗或协同作用。流式细胞仪检测发现，两药联合时细胞凋亡情况在A549细胞与A431细胞中存在明显差别。结论吉非替尼与多西他赛联合的相互作用随细胞株不同而有差异，且与序贯给药的顺序有关，其机制值得进一步研究。

Objective To observe the effects on cell proliferation,cell cycle distribution and apoptosis when sequentially administered gefitinib and docetaxel in different cell lines, and to evaluate the interaction of two drugs. Methods A431, A549, SPC-A1 and NCI-H292 cells were treated with gefitinib and docetaxel concurrently or sequentially. The anti-tumor effects were measured by growth inhibition by 3-（ 4, 5- dimethylthiazol 2-y1）-2,5-diphenyl-terazolium bromide assay. The cell cycle distribution and apoptosis of A549 and A431 celt lines were measured by flow cytometry. Results The combination of gefitinib and docetaxel had different effects in different cell lines which depended on the sequence. When cells were exposed to docetaxel followed by gefitinib, the cell survival percentage decreased in all cell lines. When gefitinib was given before or concurrently with docetaxel, the cell survival percentage decreased in A4,31 lines,which showed a synergistic effect between two drugs. Meanwhile,it increased in A549, NCI-H292 and SPC-A1 cell lines, which showed an antagonistic effect. The synergistic or antagonistic effect could be weakened by a sufficient interval between two drugs. The measurements by flow cytometry showed the apoptosis percentage in A549 and A431 cell lines were significantly different. Conclusions The combination of gefitinib and docetaxel has different effects in different cell lines which depend on the sequence. The mechanism worths further research.