Simvastatin induces growth inhibition and apoptosis in HepG2 and Huh7 hepatocellular carcinoma cells via upregulation of Notch1 expression

Huang,Xin; Ma,Jiancang; Xu,Jinkai; Su,Qinghua; Zhao,Jun

doi:10.3892/mmr.2014.2976

Simvastatin induces growth inhibition and apoptosis in HepG2 and Huh7 hepatocellular carcinoma cells via upregulation of Notch1 expression

Authors:
- Xin Huang
- Jiancang Ma
- Jinkai Xu
- Qinghua Su
- Jun Zhao
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Affiliations: Department of General Surgery, Xi'an Central Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710003, P.R. China, Department of General Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China
Published online on: November 19, 2014 https://doi.org/10.3892/mmr.2014.2976
Pages: 2334-2340

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Abstract

Statins, cholesterol‑lowering drugs, are one of the most commonly prescribed types of medications. Previous studies have suggested that simvastatin may inhibit the cell function and tumor growth of hepatocellular carcinoma (HCC) cells; however, the molecular mechanisms underlying simvastatin‑induced apoptosis in HCC cells remains to be elucidated. The aim of the present study was to investigate the role of simvastatin in the regulation of cell viability, proliferation and apoptosis in HepG2 and Huh7 HCC cells, and to elucidate the specific regulatory mechanisms by which simvastatin proceeds. MTT, trypan blue and flow cytometric analyses were performed in order to detect viability, proliferation and apoptosis in HepG2 and Huh7 cells. The results of the present study demonstrated that simvastatin significantly decreased cell viability and proliferation as well as increased apoptosis in HepG2 and Huh7 cells compared to that in untreated cells. In addition, reverse transcription quantitative polymerase chain reaction and western blot analysis revealed that simvastatin‑treated cells exhibited increased expression levles of Notch1, p53, and Bax, as well as decreased expression levels of B cell lymphoma 2; furthermore, Notch1 upregulation resulted in the inhibition of Akt phosphorylation. In conclusion, the results of the present study indicated that simvastatin significantly promoted apoptosis in HCC cells, the mechanism of which may have proceeded via the upregualtion of the Notch1 gene in the Akt‑dependent signaling pathway.

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