Vitamin D3 enhances antitumor activity of metformin in human bladder carcinoma SW-780 cells

作者:Guo Li Shu; Li Hong Xia; Li Chun Yang; Zhang Sheng Yan; Chen Jia; Wang Qi Long; Gao Jing Miao; Liang Jia Qi; Gao Ming Tang; Wu Yong Jie*
来源:Pharmazie, 2015, 70(2): 123-128.
DOI:10.1691/ph.2015.3936

摘要

Objective: To study the effects of vitamin D3 combined with metformin on the proliferation and apoptosis in human bladder cancer cell line SW-780 and its possible mechanism. Methods: MU assay and fluorescence microscope observations were used to study the effects of vitamin D3 combined with metformin on the proliferation and apoptosis of SW-780 cells in vitro. Western blot was used to detect the expression of apoptosis-related proteins p-Bcl-2, Bax, Cyclin D1, c-Myc and related signaling pathways activated proteins p-IGF-IR, p-mTOR, p-P7056K, p-S6. Results: MU results showed that 320 mu g/ml vitamin D3 combined with 620 mu g/ml metformin acting on cells for 48h had a significant synergistic effect on proliferation. Fluorescence microscope observations showed that compared with negative control group and monotherapy treatment group, the apoptosis features of combination treatment group were obvious and the apoptosis rate increased greatly. Western blot showed that compared with the negative control group and monotherapy treatment group, the expression levels of p-Bcl-2, Cyclin D-1 and c-Myc in combination treatment group significantly decreased, whereas the expression level of Bax significantly increased, and the expression levels of p-IGF-IR, p-mTOR, p-P70S6K and p-S6 in combination treatment group significantly decreased. Conclusion: Vitamin D3 combined with metformin exhibited obvious inhibitory effects on the cell proliferation and apoptosis induction in SW-780 cells. The underlying anti-tumor mechanism might be related to inhibiting the expressions of p-Bcl-2, Cyclin D1, c-Myc, p-IGF-IR, p-mTOR, p-P70S6K, p-S6 and activating the expression of Bax.