Identification of a novel autophagic inhibitor cepharanthine to enhance the anti-cancer property of dacomitinib in non-small cell lung cancer
10.3867/j.issn.1000-3002.2017.10.077
- Author:
TANG ZHENG-HAI
1
;
CAO WEN-XIANG
;
GUO XIA
;
DAI XIAO-YANG
;
LU JIA-HONG
;
CHEN XIU-PING
;
ZHU HONG
;
LU JIN-JIAN
Author Information
1. State Key Laboratory of Quality Research in Chinese Medicine
- Keywords:
cepharanthine;
non-small cell lung cancer;
autophagy;
lysosome;
dacomitinib
- From:Chinese Journal of Pharmacology and Toxicology
2017;31(10):997-998
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE Identification of novel autophagy inhibitors for the combinational treatment of non-small cell lung cancer (NSCLC). METHODS MTT assay and annexin V/PI staining assay were used to evaluate the cell proliferation and apoptosis, respectively. Immunofluorescence staining and cathepsin activity assay were used to detect autophagy. Small interfering RNA was performed to silence the genes and Western blot assay was used to evaluate the protein express levels. Xenograft experiments were applied for in vivo evaluation. RESULTS Cepharanthine, a natural compound, increased LC3-II expression and GFP-LC3 puncta formation in NSCLC NCI-H1975 cells. Numerous yellow puncta were observed in cepharanthine- treated cells with mRFP- EGFP- LC3 transfection. Co-staining of GFP-LC3 with LysoTracker red or LAMP1 antibody suggested that cepharanthine inhibits autophagosomes- lysosomes fusion. Moreover, cepharanthine attenuated the lysosomal cathepsins maturation. We also confirmed that dacomitinib induced cytoprotective autophagy. Combined treatment with cepharanthine increased the anti- cancer effects of dacomitinib in vitro and in vivo. Besides, cepharanthine could not enhance the anti-cancer effect of dacomitinib in autophagy deficient cells. CONCLUSION Cepharanthine might be further developed as a promising autophagic inhibitor, and combined treatment cepharanthine with dacomitinib could pose as an effective strategy for NSCLC treatment.
