四君子汤联合吉非替尼对非小细胞肺癌PC9细胞的协同作用及中效原理评价

Synergistic Effects of Sijunzi Decoction Combined with Gefitinib on Non-Small Cell Lung Cancer PC9 Cells and Evaluation for Principle of Intermediate Effects

目的:利用中效原理评价四君子汤与吉非替尼联合应用对非小细胞肺癌PC9细胞的协同抑制作用,并探讨其对细胞凋亡和细胞周期的影响。方法:采用CellTiter-Glo法检测四君子汤和吉非替尼对PC9细胞增殖的影响;根据中效原理使用Calcusyn软件评价两药是否具有协同作用;使用流式细胞仪检测两药对细胞凋亡和细胞周期的影响。结果:四君子汤和吉非替尼抑制PC9细胞增殖均呈剂量依赖性。两药联合作用于PC9细胞,IC_(50)由(0.75±0.26)μg/L降至(0.10±0.02)μg/L,与吉非替尼组相比,差异有统计学意义(P<0.05)。流式细胞术检测结果表明,联合用药能够通过促进细胞凋亡抑制细胞增殖,且联合用药能促进细胞的早期凋亡,处于G_(2)/M期细胞的比例与单独给药时相比,差异有统计学意义(P<0.05)。结论:四君子汤联合吉非替尼对非小细胞肺癌PC9细胞具有协同抑制作用,其协同机制可能与诱导细胞凋亡及G_(2)/M期阻滞相关。

OBJECTIVE:To evaluate the synergistic inhibitory effects of Sijunzi decoction combined with gefitinib on non-small cell lung cancer PC9 cells by using the principle of intermediate effects,and to explore its effects on cell apoptosis and cell cycle.METHODS:CellTiter-Glo method was used to detect the effects of Sijunzi decoction and gefitinib on the proliferation of PC9 cells.Calcusyn software was used to evaluate the synergistic effects of the two drugs according to the principle of intermediate effects.The flow cytometry was used to detect the effects of the two drugs on apoptosis and cell cycle.RESULTS:Sijunzi decoction and gefitinib inhibited the proliferation of PC9 cells in a dose-dependent manner.When the two drugs were used in combination on PC9 cells,the IC_(50) decreased from(0.75±0.26)μg/L to(0.10±0.02)μg/L,the difference was statistically significant compared with gefitinib alone(P<0.05).The results of flow cytometry showed that after the combination of two drugs,the proportion of apoptosis increased significantly,and the percentage of cells in the G_(2)/M phase was significantly different from that of the single drug(P<0.05).CONCLUSIONS:Sijunzi decoction combined with gefitinib have synergistic inhibitory effect on non-small cell lung cancer PC9 cells,and the synergistic mechanism may be related to the induction of apoptosis and G_(2)/M phase block.