Role of EZH2 Inhibitor Combined with Gefitinib in EGFR-TKIs Resistant Lung Cancer Cells.
10.3779/j.issn.1009-3419.2019.05.01
- Author:
Hao GONG
1
;
Yin YUAN
1
;
Yongwen LI
2
;
Hongbing ZHANG
1
;
Ying LI
2
;
Weiting LI
1
;
Pan WANG
1
;
Ruifeng SHI
1
;
Chao LIU
1
;
Liyuan CUI
1
;
Hongyu LIU
2
;
Jun CHEN
1
Author Information
1. Department of Lung Cancer Surgery, Tianjin Medical University General Hospital, Tianjin 300052, China.
2. Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin 300052, China.
- Publication Type:Journal Article
- Keywords:
Acquired resistance;
EZH2;
EZH2 inhibitor;
Gefitinib;
Lung neoplasms
- MeSH:
Antineoplastic Agents;
pharmacology;
Cell Line, Tumor;
Cell Movement;
drug effects;
Cell Proliferation;
drug effects;
Cell Survival;
drug effects;
Drug Resistance, Neoplasm;
drug effects;
Drug Synergism;
Enhancer of Zeste Homolog 2 Protein;
antagonists & inhibitors;
ErbB Receptors;
antagonists & inhibitors;
Gefitinib;
pharmacology;
Humans;
Lung Neoplasms;
pathology;
Protein Kinase Inhibitors;
pharmacology
- From:
Chinese Journal of Lung Cancer
2019;22(5):255-263
- CountryChina
- Language:Chinese
-
Abstract:
BACKGROUND:Lung cancer is one of the common malignant tumors that impair human health. With the development of epigenetics, the researchers found that enhancer of Zeste homolog 2 (EZH2) is highly expressed in lung cancer tissue and its expression is closely related to the prognosis. EZH2 inhibitor can also enhance the sensitivity of tumor cells to a variety of anti-tumor drugs. The purpose of this study is to investigate the effect of combination of EZH2 inhibitor and gefitinib on the proliferation, apoptosis and migration of Gefitinib-resistant lung cancer cells.
METHODS:PC9 and PC9/AB2 cells were used for this study. CCK-8 and EdU experiment were used to detect combined treatment on cell viability and proliferation activity; Wound healing assay and Transwell chamber experiment were used to determine the effects of combination therapy on cell migration ability; Flow cytometry was used to detect the effect of combination therapy on EZH2 and apoptosis; Western blot was used to observe the effect of combination therapy on epidermal growth factor receptor (EGFR) signaling pathway-related proteins expression.
RESULTS:In gefitinib-resistant cell line PC9/AB2, gefitinib combined with EZH2 inhibitor GSK343 can significantly inhibit cell viability, reduce cell migration and increase cell apoptosis. At the same time, combination therapy can significantly inhibit the expression of EZH2 and phosphorylation EGFR proteins.
CONCLUSIONS:The combination of EZH2 inhibitor GSK343 and gefitinib sensitize PC9/AB2 cell to gefitinib response. This study also suggests that synergistic therapy plays a role in the reversal of EGFR-tyrosine kinase inhibitor (EGFR-TKIs) resistance in lung cancer.
