Molecular mechanism underlying the anticancer effect of simvastatin on MDA‑MB‑231 human breast cancer cells

Shen,Yuan‑Yuan; Yuan,Yuan; Du,Ying‑Ying; Pan,Yue‑Yin

doi:10.3892/mmr.2015.3411

Molecular mechanism underlying the anticancer effect of simvastatin on MDA‑MB‑231 human breast cancer cells

Authors:
- Yuan‑Yuan Shen
- Yuan Yuan
- Ying‑Ying Du
- Yue‑Yin Pan
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Affiliations: Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China, The Central Laboratory of Binhu Hospital, The Third Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230601, P.R. China
Published online on: March 4, 2015 https://doi.org/10.3892/mmr.2015.3411
Pages: 623-630

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Abstract

Breast carcinoma is the leading cause of cancer‑associated mortality in female individuals worldwide. Previous studies have investigated the pro‑apoptotic and antimetastatic effects of statins, and have demonstrated that simvastatin exhibits antitumor activity and potent chemopreventive effects. However, the mechanism underlying the effects of simvastatin in breast cancer remains to be elucidated. The present study demonstrated that simvastatin inhibited the proliferation of MDA‑MB‑231 human breast cancer cells in a dose‑dependent manner, decreased the protein expression of B cell lymphoma 2 (Bcl‑2) and increased the protein expression of Bcl‑2‑associated X protein in time‑ and dose‑dependent manners. In addition, simvastatin arrested cells in the G0/G1 phase of the cell cycle, downregulated the protein expression levels of cyclin D1 and cyclin‑dependent kinase (CDK)2, mediated the mitochondria‑dependent caspase cascade by increasing the protein expression levels of caspase‑3, ‑8 and ‑9, and downregulated the protein expression of X‑linked inhibitor of apoptosis, which induced cell apoptosis. In addition, simvastatin decreased the protein expression of matrix metalloproteinase (MMP)‑2 and suppressed the activation of nuclear factor (NF)‑κB in the MDA‑MB‑231 cells. Taken together, these results demonstrated that the antitumor effect of simvastatin in the human MDA‑MB‑231 breast cancer cell line was via the inhibition of cell proliferation, affecting the cell cycle, downregulating the expression levels of cyclin D1 and CDKs, inducing apoptosis and decreasing the expression of MMP‑2, possibly by inhibiting the activation of NF‑κB. Statin treatment may provide a novel therapeutic approach for the treatment of breast cancer.

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