Effective Combined Treatment with Aqueous Extract of Taxus chinensis var.mairei (AETC) and Gefitinib in Inhibiting Non-Small Cell Lung Cancer PC9, PC9/R Cell Lines In Vitro and In Vivo
Objective: Explore the effects and mechanism of AETC combined with Gefitinib in inhibiting non-small cell lung cancer PC9/R cell lines in vitro and in vivo. Methods: Culture human lung adenocarcinoma cell lines PC9/R, PC9 and establish nude mice models. MTT was used to measure the inhibition of cell proliferation. Xenografts' volume of each treatment group was measured every 3 days and the weight of tumors was measured after sacrifice of mice. Western-blot was used to test the expression of EGFR, p-EGFR, ERK1/2, p-ERK1/2, PI3K, AKT, p-AKT, STAT3, p-STAT3 protein in cells and xenografted tumors. PCR was used to test the expression of EGFR, ERK1, ERK2, PI3K, AKT, STAT3 mRNA. One-way analysis of variance of each group was performed by SPSS 19.0 software. Results: AETC in combination with certain concentration of gefitinb manifests better affection than single drug (compared with Gefitinib, P<0.05) in PC9 and PC9/R cells, which shows the 2 drugs have synergistic effect. AETC plus Gefitinib can achieve better inhibitory effect in the growth of PC9/R induced xenografts than Gefitinib alone (P<0.05) through decreasing the expression of EGFR and its downstream pathways related proteins and mRNAs in vivo and in vitro. AETC alone can inhibit EGFR and its downstream pathways to reach anti-tumor effects in PC9 and PC9/R cell lines. Conclusions: AETC plus Gefitinib is effective in overcoming Gefitinib resistance in PC9/R cell lines in vivo and in vitro through suppressing EGFR and its downstream pathways. AETC alone can reach anti-tumor effects in PC9 and PC9/R cell lines through inhibiting EGFR and its downstream pathways.
Qijin Shu, Anqi Li, Zhiqiang Wu, Ji Jiang, Yangyang Song, Xinyun Li, Wei Wu, and Lu Zhang