Combination treatment of Src inhibitor Saracatinib with GMI, aGanoderma microsporumimmunomodulatory protein, induce synthetic lethality via autophagy and apoptosis in lung cancer cells

被引：11

作者：

Chiu, Ling-Yen ^{[1
,2
]}

Hsin, I-Lun ^{[1
]}

Tsai, Jen-Ning ^{[3
,4
]}

Chen, Chih-Jung ^{[1
,5
]}

Ou, Chu-Chyn ^{[6
]}

Wu, Wen-Jun ^{[1
]}

Sheu, Gwo-Tarng ^{[1
]}

Ko, Jiunn-Liang ^{[1
,7
,8
]}

机构：

[1] Chung Shan Med Univ, Inst Med, 110,Sec 1,Chien Kuo N Rd, Taichung 40203, Taiwan

[2] Natl Taiwan Univ Sport, Dept Exercise Hlth Sci, Taichung, Taiwan

[3] Chung Shan Med Univ, Dept Med Lab & Biotechnol, Taichung, Taiwan

[4] Chung Shan Med Univ Hosp, Clin Lab, Taichung, Taiwan

[5] Taichung Vet Gen Hosp, Dept Pathol & Lab Med, Taichung, Taiwan

[6] Chung Shan Med Univ, Sch Nutr, Taichung, Taiwan

[7] Chung Shan Med Univ Hosp, Dept Internal Med, Div Med Oncol, Taichung, Taiwan

[8] Chung Shan Med Univ, Sch Med, Taichung, Taiwan

来源：

JOURNAL OF CELLULAR PHYSIOLOGY | 2021年 / 236卷 / 02期

关键词：

apoptosis; autophagy; GMI; saracatinib; Src; PHASE-II TRIAL; IMMUNOMODULATORY PROTEIN; GANODERMA-MICROSPORUM; ANTITUMOR-ACTIVITY; KINASE INHIBITOR; PATHWAY; ACTIVATION; MIGRATION; TARGETS; MODELS;

D O I：

10.1002/jcp.29924

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Saracatinib is an oral Src-kinase inhibitor and has been studied in preclinical models and clinical trials of cancer therapy. GMI, a fungal immunomodulatory protein fromGanoderma microsporum, possesses antitumor capacity. The aim of this study is to evaluate the cytotoxic effect of combination treatment with saracatinib and GMI on parental and pemetrexed-resistant lung cancer cells. Cotreatment with saracatinib and GMI induced synergistic and additive cytotoxic effect in A549 and A400 cells by annexin V/propidium iodide assay and combination index. Using western blot assay, saracatinib, and GMI combined treatment synergistically induced caspase-7 activation in A549 cells. Different from A549 cells, saracatinib and GMI cotreatment markedly increased LC3B-II in A400 cells. ATG5 silencing abolished the caspase-7 activation and reduced cell death in A549 cells after cotreatment. This is the first study to provide a novel strategy of treating lung cancer with or without drug resistance via combination treatment with GMI and saracatinib.

引用

页码：1148 / 1157

页数：10

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