Objective       To determine the effect and underlying mechanism of autophagy on the apoptosis in gefitinib-induced non-small cell lung cancer cell (NSCLC) line PC-9 with epidermal growth factor receptor (EGFR)-mutation.       Methods       MTT assay was applied to assess cell viability in PC-9 cells after gefitinib treatment. Acridine orange staining was used to detect the formation of acidic vesicular organelles (AVOs) after the treatment. Western blot analysis was used to determine the expression of autophagy marker LC3

apoptosis-related proteins PARP

Caspase-3 and cleaved Caspase-3

and signal pathway proteins Akt and mTOR. Flow cytometry was used to measure the apoptosis in presence or absence of autophagy inducer rapamycin.       Results       Gefitinib treatment inhibited cell growth and induced cell apoptosis in a dose-dependent manner in PC-9 cells shown by MTT assay and flow cytometry

enhanced autophagy for more AVOs formed by acridine orange staining

and significantly upregulated LC3. Gefitinib in combination with rapamycin promoted cytotoxic effect of gefitinib to PC-9 cells and down-regulated Akt/mTOR phosphorylation.       Conclusion       Gefitinib induces autophagy in PC-9 cells

and induction autophagy facilitates gefitinib-induced apoptosis.