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  • Synergistic antitumor activity of vitamin D3 combined with metformin in human breast carcinoma MDA-MB-231 cells involves m-TOR related signaling pathways.

Synergistic antitumor activity of vitamin D3 combined with metformin in human breast carcinoma MDA-MB-231 cells involves m-TOR related signaling pathways.

Die Pharmazie (2015-05-23)
Li-Shu Guo, Hong-Xia Li, Chun-Yang Li, Sheng-Yan Zhang, Jia Chen, Qi-Long Wang, Jing-Miao Gao, Jia-Qi Liang, Ming-Tang Gao, Yong-Jie Wu
ABSTRACT

Metformin is usually used for the treatment of type 2 diabetes. Recently, many studies suggest that metformin and vitamin D have broad-spectrum antitumor activities. Our aim in this research was to study the effects of vitamin D3 combined with metformin on the apoptosis induction and its mechanisms in the human breast cancer cell line MDA-MB-231. Cell proliferation was measured by methylthiazol tetrazolium (MTT) assay. The morphology of cell apoptosis was observed after Hoechst 33342 staining. Here we show that vitamin D3 280 μg/ml or vitamin D3 300 μg/ml or vitamin D3 320 μg/ml seperately combined with metformin 15000 μg/ml exhibited synergistic effects on cell proliferation and apoptosis. The underlying anti-tumor mechanisms may involve m-TOR related pathways, which are related to activating expression of cleaved caspase-3, Bax and p-AMPK, as well as inhibiting expressions of p-Bcl-2, c-Myc, p-IGF-IR, p-mTOR, p-P70S6K, p-S6.

MATERIALS
Product Number
Brand
Product Description

Supelco
Cholecalciferol (Vitamin D3), Pharmaceutical Secondary Standard; Certified Reference Material
Cholecalciferol for system suitability, European Pharmacopoeia (EP) Reference Standard
Supelco
Vitamin D3 solution, 1 mg/mL in ethanol, ampule of 1 mL, certified reference material, Cerilliant®
Sigma-Aldrich
Cholecalciferol, analytical standard
Sigma-Aldrich
Cholecalciferol, meets USP testing specifications
Sigma-Aldrich
Cholecalciferol, ≥98% (HPLC)
Supelco
Metformin hydrochloride, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
1,1-Dimethylbiguanide hydrochloride, 97%
Supelco
Cholecalciferol (D3), analytical standard
Cholecalciferol, European Pharmacopoeia (EP) Reference Standard