Vitamin D3 potentiates the growth inhibitory effects of metformin in DU145 human prostate cancer cells mediated by AMPK/mTOR signalling pathway

Summary Metformin and vitamin D3 both exhibit a strong antiproliferative action in numerous cancer cell lines, including in human prostate cancer cells. Here we showed that the combination of the two drugs had a much stronger effect on DU145 human prostate cancer cell growth than either drug alone....

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Bibliographic Details
Published in:Clinical and experimental pharmacology & physiology 2015-06, Vol.42 (6), p.711-717
Main Authors: Li, Hong-Xia, Gao, Jing-Miao, Liang, Jia-Qi, Xi, Jun-Min, Fu, Meng, Wu, Yong-Jie
Format: Article
Language:English
Subjects:
AMP-Activated Protein Kinases - physiology
Apoptosis
Cell cycle
Cell Cycle - drug effects
Cell Cycle - physiology
Cell growth
Cell Line, Tumor
cell proliferation
Cholecalciferol - administration & dosage
Dose-Response Relationship, Drug
Drug Synergism
Growth Inhibitors - administration & dosage
Humans
Male
metformin
Metformin - administration & dosage
Prostate cancer
Prostatic Neoplasms - drug therapy
Prostatic Neoplasms - metabolism
Signal Transduction - drug effects
Signal Transduction - physiology
synergism
TOR Serine-Threonine Kinases - physiology
vitamin D3
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Summary:Summary Metformin and vitamin D3 both exhibit a strong antiproliferative action in numerous cancer cell lines, including in human prostate cancer cells. Here we showed that the combination of the two drugs had a much stronger effect on DU145 human prostate cancer cell growth than either drug alone. In this research, cell proliferation was measured by methylthiazol tetrazolium (MTT) assay. Cell apoptosis was determined with Hoechst 33342 staining. Western blotting and cell cycle analyses were used to elucidate potential mechanisms of interaction between the drugs. It is shown that in cultured DU145 cells, vitamin D3 combined with metformin exhibits synergistic effects on cell proliferation and apoptosis. The underlying antitumor mechanisms may involve altered cycle distribution with a G1/S cell cycle arrest, activation of phospho‐AMPK with subsequent inhibition of downstream mTOR signalling pathway, down‐regulate c‐Myc expression, and reducing the level of anti‐apoptotic protein p‐Bcl‐2. In conclusion, metformin and vitamin D3 synergistically inhibit DU145 cell growth, indicating a promising clinical therapeutic strategy for the treatment of androgen‐independent prostate cancer.
ISSN:0305-1870
1440-1681
DOI:10.1111/1440-1681.12409