TY - JOUR T1 - Tetrandrine Increases the Sensitivity of Human Lung Adenocarcinoma PC14 Cells to Gefitinib by Lysosomal Inhibition JF - Anticancer Research JO - Anticancer Res SP - 6585 LP - 6593 DO - 10.21873/anticanres.13874 VL - 39 IS - 12 AU - EIKO SATO AU - SINYA OHTA AU - KENJIRO KAWAKAMI AU - MANA IKEDA AU - TATSUO TAKAHASHI AU - SHINJIRO KOBAYASHI AU - MASAAKI NOMURA Y1 - 2019/12/01 UR - http://ar.iiarjournals.org/content/39/12/6585.abstract N2 - 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. ER -