Atorvastatin negatively regulates MAPK pathway in vitro to inhibit proliferation, migration, and invasion of hepatocellular carcinoma cells

阿托伐他汀在体外通过负调控MAPK通路抑制肝细胞癌细胞的增殖、迁移和侵袭。

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Abstract

Hepatocellular carcinoma (HCC) is a prevalent type of tumor. Given the controversy surrounding atorvastatin and HCC, we conducted this study to determine whether atorvastatin has anticancer activity against HCC. The impact of varying concentrations of atorvastatin (ATO) on the biological function of HCC cells was studied in vitro, high-throughput mRNA assays on cells and tumor tissue. Finally, an examination was conducted to assess the correlation between the ATO and the prognosis of HCC. ATO significantly inhibited the proliferation, migration, and invasiveness of HCC cells. Furthermore, in vivo, animal experiments showed that a high-fat diet facilitated the progression of HCC and that ATO did not effectively counteract these detrimental consequences. Tumor sequencing of cells and normal diet mice revealed the disparities were primarily concentrated in the MAPK signaling pathway. Western blot demonstrated ATO reduced the expression of levels of p-MEK, p-RAF1, p-P38, p-ERK, and p-JNK proteins in HCC cells compared to controls. Clinical data showed that HCC patients with ATO exhibited improved recurrence-free survival (RFS) and overall survival (OS). Following the utilization of propensity score, HCC patients with ATO were found to have better OS, whereas there was no substantial difference in RFS. Atorvastatin effectively inhibits the proliferation, invasion, and migration of HCC cells in vitro through the MAPK pathway. Additionally, ATO may help improve the prognosis of some individuals with HCC.

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