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Objective To explore the influence of epithelial mesenchymal transition(EMT)in radiosensi-tivity of EGFR-mutant NSCLC cell with acquired resistance to EGFR-TKI. Methods In this study,EGFR-mutant human lung adenocarcinoma cell line PC-9 and Gefitinib acquired resistance cell line PC-9/AB were used. Western blot was used to assess EMT. Wound healing migration assay was tested. CCK8,colony formation and flow cytome-try were used to evaluate survival fraction ,as the sensitivity to irradiation. Results PC-9/AB displayed radioresis-tance(P<0.05). When EMT was reversed with CDH1,its radiosensitivity was significantly higher than PC-9/AB (P < 0.05). PC-9/TGF also displayed radioresistance (P < 0.05),as well as EMT phenotype presented. Conclusion EMT enhanced the radioresistance of EGFR-mutant NSCLC cell with acquired resistance to EGFR-TKI, possibly through TGF-βpathway.
RESUMEN
OBJECTIVES: The aim of this study was whether quercetin induces cell death by caspase and MAPK signaling pathway in EGFR mutant lung cancer cells. METHODS: PC-9 cells, EGFR mutant lung cancer cells, were treated various times and concentrations of quercetin and harvested and measured using MTT assay, DNA fragmentation, Western blotting, and FACS analysis. RESULTS: Treatment with quercetin in PC-9 cells resulted in inhibition of cell growth through apoptosis. Quercetin-induced apoptosis was associated with caspase-dependent manner. Quercetin also significantly increased levels of phosphor-p38 and decreased levels of phosphor-ERK, indicating that quercetin induces p38 MAPK signaling pathway in PC-9 cells. Quecetin treatment also generated the release of cytochrome c in PC-9 cells; however, pretreatment with rotenone or z-LEHD-fmk, significantly attenuated quercetin-induced apoptosis. CONCLUSIONS: Our data indicate that quercetin exhibits EGFR mutant lung cancer effects through apoptosis by caspase dependent and mitochondrial pathway.