Effect of the SIRT3-AMPK/PPAR pathway on invasion and migration of cervical cancer cells

Int J Clin Exp Pathol. 2020 Oct 1;13(10):2495-2501. eCollection 2020.

Abstract

SIRT3 is a mitochondrial deacetylation protein that can promote the invasion and migration of cancer cells. We explored the effects of SIRT3 regulation of the AMPK/PPAR signaling pathway on triglycerides and the invasion and metastasis of cervical cancer cells. Immunohistochemical methods were used to detect SIRT3. The expression of AMPK and PPAR proteins in different cervical lesions was analyzed in combination with clinicopathological parameters. qRT-PCR and western blotting were used to determine the expression levels of SIRT3 in the C33a and SiHa cervical cancer cell lines. To observe the effects of altering SIRT3 levels by lentivirus transfection and the consequent changes in AMPK and PPAR protein expression, oil red O staining was used to determine intracellular triglycerides, and scratch assays and Transwell chamber experiments were performed to evaluate cervical cancer cell migration and invasion. Our data indicate that SIRT3, AMPK, and PPAR protein expression levels show an increasing trend with cervical lesion severity and are related to the degree of lymph node metastasis and differentiation; moreover, increased expression of SIRT3 can promote the expression of AMPK and PPAR proteins, is beneficial to the formation of intracellular neutral fat, and enhances the ability of cells to metastasize and invade. Our results suggest that SIRT3 activates AMPK/PPAR signaling pathways involved in cancer lipid metabolism and promotes metastasis and cell invasion.

Keywords: AMPK; PPAR; SIRT3; cervical cancer; lipid metabolism.