PMID- 37937302
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231109
IS  - 2211-8020 (Print)
IS  - 2211-8039 (Electronic)
IS  - 2211-8020 (Linking)
VI  - 13
IP  - 2
DP  - 2023
TI  - Metformin induces autophagy of cisplatin-resistant human gastric cancer cells in 
      addition to apoptosis.
PG  - 14-23
LID - 10.37796/2211-8039.1408 [doi]
AB  - Metformin has been used to treat cases of type 2 diabetes mellitus, and mounting 
      studies have shown that metformin can act alone or in synergy with other 
      anticancer agents to achieve anti-cancer efficacies on various types of tumors. 
      However, the role of metformin in either inducing autophagy and 
      cisplatin-resistance of human gastric cancer (GC) cells has never been examined. 
      The study has established a cisplatin-resistant GC cell line and investigated the 
      effects of metformin on inducing autophagy on it. The results demonstrated that 
      treatment with metformin can concentration-dependently suppress the cell 
      viability and cell confluence of cisplatin-resistant GC cells, while having no 
      effects on human primary stomach epithelial cells (HPSEC). For the first time, we 
      found that metformin can significantly increase the acidic vesicular organelles 
      (AVO) level and decrease the acridine orange (AO) level spontaneously in the 
      cisplatin-resistant GC cells. Thus, we further checked the other markers, Atg5, 
      Atg12 and LC3-II, which showed that metformin indeed induced autophagy in the 
      cisplatin-resistant GC cells. In addition, treatment of 3-Methyladenine (3-MA) 
      can significantly rescue the metformin-induced autophagy. At the same time, 
      metformin can induce the alterations of apoptosis-associated signal molecules, 
      such as caspase-3 and caspase-7 activities. Overall, the pilot study provided 
      evidence for metformin induced autophagy in addition to apoptosis, making it as 
      an effective anticancer drug for the therapy of cisplatin-resistant GC. Killing 
      the cisplatin-resistant GC cells with non-toxic metformin via both autophagy and 
      apoptosis might extend its usefulness in our fighting with chemo-resistance of 
      gastric cancer cells.
CI  - (c) the Author(s).
FAU - Fang, Chih-Wun
AU  - Fang CW
AD  - Division of Pharmacy, Zuoying Branch of Kaohsiung Armed Forces General Hospital, 
      Kaohsiung, Taiwan.
FAU - Yang, Jai-Sing
AU  - Yang JS
AD  - Department of Medical Research, China Medical University Hospital, China Medical 
      University, Taichung, Taiwan.
FAU - Chiang, Jo-Hua
AU  - Chiang JH
AD  - Department of Nursing, Chung-Jen Junior College of Nursing, Health Sciences and 
      Management, Chiayi, Taiwan.
FAU - Shieh, Po-Chuen
AU  - Shieh PC
AD  - Department of Pharmacy, Tajen University, Pingtung, Taiwan.
FAU - Tsai, Fuu-Jen
AU  - Tsai FJ
AD  - School of Chinese Medicine, College of Chinese Medicine, China Medical 
      University, Taichung, Taiwan.
AD  - China Medical University Children's Hospital, China Medical University, Taichung, 
      Taiwan.
FAU - Tsai, Chia-Wen
AU  - Tsai CW
AD  - Department of Medical Research, China Medical University Hospital, China Medical 
      University, Taichung, Taiwan.
FAU - Chang, Wen-Shin
AU  - Chang WS
AD  - Department of Medical Research, China Medical University Hospital, China Medical 
      University, Taichung, Taiwan.
LA  - eng
PT  - Journal Article
DEP - 20230601
PL  - China (Republic : 1949- )
TA  - Biomedicine (Taipei)
JT  - BioMedicine
JID - 101611451
PMC - PMC10627204
OTO - NOTNLM
OT  - Autophagy
OT  - Cisplatin-resistance
OT  - Gastric cancer
OT  - Metformin
COIS- Conflict of interest The authors declare that they have no competing interests.
EDAT- 2023/11/08 06:42
MHDA- 2023/11/08 06:43
PMCR- 2023/06/01
CRDT- 2023/11/08 04:07
PHST- 2023/02/12 00:00 [received]
PHST- 2023/02/23 00:00 [revised]
PHST- 2023/02/23 00:00 [accepted]
PHST- 2023/11/08 06:43 [medline]
PHST- 2023/11/08 06:42 [pubmed]
PHST- 2023/11/08 04:07 [entrez]
PHST- 2023/06/01 00:00 [pmc-release]
AID - bmed-13-02-014 [pii]
AID - 10.37796/2211-8039.1408 [doi]
PST - epublish
SO  - Biomedicine (Taipei). 2023 Jun 1;13(2):14-23. doi: 10.37796/2211-8039.1408. 
      eCollection 2023.