Chloride intracellular channel 1 regulates the antineoplastic effects of metformin in gallbladder cancer cells

Autor: Shili Chen, Zheng Wang, Fatao Liu, Ruiyan Yuan, Yajuan Hao, Yijian Zhang, Yong-Chen Liu, Yi Xu, Yuanyuan Ye, Lin Jiang, Yunpeng Jin, Yichi Zhang, Yingbin Liu, Wenguang Wu, Maolan Li, Yunping Hu
Jazyk: angličtina
Rok vydání: 2017
Předmět:
0301 basic medicine
Cancer Research
medicine.medical_specialty
endocrine system diseases
Cell Survival
proliferation
Down-Regulation
chloride intracellular channel 1
Antineoplastic Agents
03 medical and health sciences
0302 clinical medicine
Downregulation and upregulation
Chloride Channels
Internal medicine
Cell Line
Tumor
medicine
Humans
Gallbladder cancer
Cell Proliferation
Cell growth
Chemistry
digestive
oral
and skin physiology
apoptosis
Cancer
nutritional and metabolic diseases
General Medicine
Original Articles
medicine.disease
Metformin
Up-Regulation
030104 developmental biology
Endocrinology
Drug Discovery and Delivery
Oncology
Proto-Oncogene Proteins c-bcl-2
Apoptosis
030220 oncology & carcinogenesis
Cancer research
Original Article
Gallbladder Neoplasms
Signal transduction
gallbladder carcinoma
Proto-Oncogene Proteins c-akt
Intracellular
medicine.drug
Signal Transduction
Zdroj: Cancer Science
ISSN: 1349-7006
1347-9032
Popis: Metformin is the most commonly used drug for type 2 diabetes and has potential benefit in treating and preventing cancer. Previous studies indicated that membrane proteins can affect the antineoplastic effects of metformin and may be crucial in the field of cancer research. However, the antineoplastic effects of metformin and its mechanism in gallbladder cancer (GBC) remain largely unknown. In this study, the effects of metformin on GBC cell proliferation and viability were evaluated using the Cell Counting Kit-8 (CCK-8) assay and an apoptosis assay. Western blotting was performed to investigate related signaling pathways. Of note, inhibition, knockdown and upregulation of the membrane protein Chloride intracellular channel 1 (CLIC1) can affect GBC resistance in the presence of metformin. Our data demonstrated that metformin apparently inhibits the proliferation and viability of GBC cells. Metformin promoted cell apoptosis and increased the number of early apoptotic cells. We found that metformin can exert growth-suppressive effects on these cell lines via inhibition of p-Akt activity and the Bcl-2 family. Notably, either dysfunction or downregulation of CLIC1 can partially decrease the antineoplastic effects of metformin while upregulation of CLIC1 can increase drug sensitivity. Our findings provide experimental evidence for using metformin as an antitumor treatment for gallbladder carcinoma.
Databáze: OpenAIRE
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