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Publication
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| Title of Article |
Metformin enhances cisplatin induced inhibition of cholangiocarcinoma cells via AMPK-mTOR pathway |
| Date of Acceptance |
26 May 2018 |
| Journal |
| Title of Journal |
Life Sciences |
| Standard |
ISI |
| Institute of Journal |
2018 Elsevier B.V. |
| ISBN/ISSN |
doi.org/10.1016/j.lfs.2018.05.046 |
| Volume |
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| Issue |
207 |
| Month |
August |
| Year of Publication |
2018 |
| Page |
172-183 |
| Abstract |
Aims: AMP-activated protein kinase (AMPK) functions as a cellular energy sensor regulating various aspects of cellular metabolism. Metformin (Met), an activator of AMPK, has been reported to reduce the cancer risk and enhance antitumor effects in certain cancers. Cholangiocarcinoma (CCA) is an aggressive malignancy which rarely responds to chemotherapeutic agents. We investigated the chemosensitizing effects of Met in CCA cells.
Materials and methods: KKU-100 and KKU-452 cells were used in the study. Antiproliferation of Met and cisplatin
(Cis) was analyzed by sulforhodamine B and colony forming assays. Apoptotic cell death was analyzed by acridine
orange and ethidium bromide staining method. Cell cycle analysis was performed by flow cytometric
method. Effects on cell migration and invasion were analyzed by wound healing assay and transwell chamber
method. Expression of proteins was examined by western blot analysis.
Key findings: Met enhanced the antiproliferation of Cis, and conferred antimigration and anti-invasion in CCA
cells, where Cis alone did not have two latter effects. This chemosensitizing effect is related to the activation of
AMPK and suppression of Akt, mTOR and p70S6K. Met and Cis increased expression of p53 and p21 and suppressed
expression of cyclin D1. This effect was associated with cell cycle arrest at S phase. The anti-invasion
effect was casually associated with the suppression of FAK expression. The cytotoxic effect of the drug combination
was mimicked by AICAR, an AMPK agonist.
Significance: Met may be a novel agent to increase the efficacy of Cis to treat CCA. |
| Keyword |
Metformin, AMPK ,Cholangiocarcinoma, Chemosensitizing effect, Migration |
| Author |
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| Reviewing Status |
มีผู้ประเมินอิสระ |
| Status |
ตีพิมพ์แล้ว |
| Level of Publication |
นานาชาติ |
| citation |
true |
| Part of thesis |
true |
| Attach file |
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| Citation |
0
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Journal Publication
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