The Zuo Jin Wan Formula increases chemosensitivity of human primary gastric cancer cells by AKT mediated mitochondrial translocation of cofilin-1.
10.1016/S1875-5364(19)30022-6
- Author:
Meng-Yao SUN
1
;
Dan-Dan WANG
2
;
Jian SUN
3
;
Xiao-Hua ZHAO
2
;
Si CAI
1
;
Qiu-Xue WU
1
;
Tao JIE
1
;
Zhen-Hua NI
1
;
Jian-Yue SUN
4
;
Qing-Feng TANG
5
Author Information
1. Department of Clinical Laboratory and Central Laboratory, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China.
2. Institute of Interdisciplinary Medical Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
3. Department of Clinical Laboratory, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200021, China.
4. Department of Pediatrics, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China. Electronic address: sunjianyue@126.com.
5. Department of Clinical Laboratory and Central Laboratory, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China. Electronic address: tangqingfeng126@126.com.
- Publication Type:Journal Article
- Keywords:
AKT;
Chemoresistance;
Primary GC cells;
ZJW
- MeSH:
Adult;
Aged;
Aged, 80 and over;
Apoptosis;
drug effects;
Cell Proliferation;
drug effects;
Cisplatin;
pharmacology;
therapeutic use;
Cofilin 1;
metabolism;
Drug Resistance, Neoplasm;
drug effects;
Drugs, Chinese Herbal;
pharmacology;
Female;
Humans;
Male;
Middle Aged;
Mitochondria;
drug effects;
metabolism;
pathology;
Proto-Oncogene Proteins c-akt;
metabolism;
Proto-Oncogene Proteins c-bcl-2;
metabolism;
Stomach Neoplasms;
drug therapy;
metabolism;
pathology;
Tumor Cells, Cultured
- From:
Chinese Journal of Natural Medicines (English Ed.)
2019;17(3):198-208
- CountryChina
- Language:English
-
Abstract:
Resistance to cisplatin (DDP)-based chemotherapy is a major cause of treatment failure in human gastric cancer (GC). It is necessary to identify the drugs to re-sensitize GC cells to DDP. In our previous research, Zuo Jin Wan Formula (ZJW) has been proved could increase the mitochondrial apoptosis via cofilin-1 in a immortalized cell line, SGC-7901/DDP. Due to the immortalized cells may still difficult highly recapitulate the important molecular events in vivo, primary GC cells model derived from clinical patient was constructed in the present study to further evaluate the effect of ZJW and the underlying molecular mechanism. Immunofluorescent staining was used to indentify primary cultured human GC cells. Western blotting was carried out to detect the protein expression. Cell Counting Kit-8 (CCK-8) was used to evaluate cell proliferation. Flow cytometry analysis was performed to assess cell apoptosis. ZJW inhibited proliferation and induced apoptosis in primary DDP-resistant GC cells. Notably, the apoptosis in GC cells was mediated by inducing cofilin-1 mitochondrial translocation, down-regulating Bcl-2 and up-regulating Bax expression. Surprisingly, the level of p-AKT protein was higher in DDP-resistant GC cells than that of the DDP-sensitive GC cells, and the activation of AKT could attenuate ZJW-induced sensitivity to DDP. These data revealed that ZJW can increase the chemosensitivity in DDP-resistant primary GC cells by inducing mitochondrial apoptosis and AKT inactivation. The combining chemotherapy with ZJW may be an effective therapeutic strategy for GC chemoresistance patients.
