RT Journal Article SR Electronic T1 Tetrandrine Increases the Sensitivity of Human Lung Adenocarcinoma PC14 Cells to Gefitinib by Lysosomal Inhibition JF Anticancer Research JO Anticancer Res FD International Institute of Anticancer Research SP 6585 OP 6593 DO 10.21873/anticanres.13874 VO 39 IS 12 A1 EIKO SATO A1 SINYA OHTA A1 KENJIRO KAWAKAMI A1 MANA IKEDA A1 TATSUO TAKAHASHI A1 SHINJIRO KOBAYASHI A1 MASAAKI NOMURA YR 2019 UL http://ar.iiarjournals.org/content/39/12/6585.abstract AB Background/Aim: Human lung adenocarcinoma PC14 cells without mutations in the epidermal growth factor receptor (EGFR) are less sensitive to gefitinib than PC9 cells with EGFR mutations. We report the involvement of tetrandrine in autophagy flux as a mechanism that enhances the sensitivity of PC14 cells to gefitinib. Materials and Methods: Sensitivity to gefitinib was determined by a growth inhibition assay, and quantitative real-time PCR, western blotting, and fluorescent immunostaining were used to detect autophagy. Results: In PC14 cells, combined treatment with gefitinib and tetrandrine caused a significant increase in gefitinib sensitivity and autophagy-related mRNAs and proteins (LC3, etc.), and the LC3 protein accumulated in lysosomes. Furthermore, an autophagy flux assay revealed that tetrandrine inhibited lysosomes and that gefitinib promoted autophagy. Finally, the sensitivity of PC14 cells to gefitinib was enhanced with chloroquine. Conclusion: Tetrandrine possibly increases the susceptibility of PC14 cells to gefitinib by lysosomal inhibition.