Lovastatin inhibits the proliferation of HNSCC cells by downregulating the MCM complex after PPARγ activation

Abstract

Abstract Purpose Statins have a protective effect overall cancer risk. However, the effect of lovastatin on head and neck squamous cell carcinoma (HNSCC) and the underlying mechanism remain unclear. Here, we focused on the potential role of PPARγ in the lovastatin-mediated inhibition of malignant development in HNSCC. Methods The postoperative survival of HNSCC patients treated with or without lovastatin was statistically analyzed, and the expression of Ki67 was detected via immunohistochemistry. EdU expression in the tumor tissue of nude mice was detected by immunofluorescence. The proliferation and migration of HNSCC cells were detected by CCK-8, scratch healing and Transwell assays. Cell apoptosis and cell cycle distribution were detected via flow cytometry. The expression levels of PPARγ and MCM in cells and human HNSCC tissues were detected by western blotting and immunohistochemistry, respectively. The contribution of PPARγ to the effect of lovastatin on HNSCC was verified by treatment with a PPARγ antagonist (GW9662) and PPARγ knockdown. Results A case‒control study revealed that patients who used lovastatin had a better prognosis and lower Ki67 expression in tumor tissues than patients who did not receive lovastatin. Lovastatin also inhibited HNSCC growth in nude mice (n = 5) and decreased EdU expression in tumors. Lovastatin inhibited proliferation by activating PPARγ and downregulating MCM complexes in HNSCC cells. In addition, after PPARγ activation, lovastatin inhibited migration and enhanced the cisplatin sensitivity of CaL-27 cells. Conclusions Our findings suggest that PPARγ may be a target of lovastatin in inhibiting the proliferation of HNSCC cells and improving patient prognosis.