# SIRT1 regulates glycolysis and angiogenesis of ovarian cancer through β-catenin/c-Myc/PKM2, and its mechanism in chemotherapy resistance

## TL;DR

This study shows that SIRT1 promotes ovarian cancer growth and drug resistance by boosting glycolysis and blood vessel formation through a specific molecular pathway.

## Contribution

The study identifies SIRT1 as a novel target for ovarian cancer treatment by linking it to chemotherapy resistance via β-catenin/c-Myc/PKM2 signaling.

## Key findings

- SIRT1 is overexpressed in cisplatin-resistant ovarian cancer cells and promotes chemotherapy resistance.
- SIRT1 activates glycolysis and angiogenesis through the β-catenin/c-Myc/PKM2 pathway in ovarian cancer cells.
- Knocking down SIRT1 reduces tumor growth, glycolysis, and angiogenesis in mouse models.

## Abstract

The purpose of this study is to explore the molecular mechanism of SIRT1 regulating chemotherapy resistance.

Expression level of SIRT1 in ovarian cancer cell lines SKOV3, SKOV3/DDP (cisplatin-resistant cell line) and normal ovarian epithelial cell line IOSE80 was detected. Through the intervention of β-catenin agonist BML-284, the mechanism of SIRT1 regulating glycolysis and angiogenesis through β-catenin/c-myc/PKM2 pathway was discussed. Finally, the nude mice transplanted tumor model was constructed to verify the role of SIRT1 in vivo.

The expression of SIRT1 increased in ovarian cancer cell line, especially in cisplatin-resistant cell line SKOV3/DDP. Knocking down SIRT1 can inhibit the proliferation, invasion and migration of ovarian cancer cells, promote cell apoptosis, and reduce the drug resistance of cells to cisplatin. SIRT1 enhances the malignant biological behavior of ovarian cancer cells by promoting glycolysis and angiogenesis. SIRT1 up-regulates the expression of key glycolytic enzymes and angiogenic factors by activating β-catenin/c-myc/PKM2 pathway. In vivo experiments, knocking down SIRT1 can reduce the glycolysis level and angiogenesis ability of tumor tissue.

SIRT1 promotes glycolysis and angiogenesis of ovarian cancer cells by activating β-catenin/c-myc/PKM2 pathway, thus enhancing chemotherapy resistance. SIRT1 is expected to be a new target for ovarian cancer treatment.