Combination of paclitaxel with rosiglitazone induces synergistic cytotoxic effects in ovarian cancer cells

Sci Rep. 2024 Dec 28;14(1):30672. doi: 10.1038/s41598-024-74277-9.

Abstract

Ovarian cancer is known to be a challenging disease to detect at an early stage and is a major cause of death among women. The current treatment for ovarian cancer typically involves a combination of surgery and the use of drugs such as platinum-based cytotoxic agents, anti-angiogenic drugs, etc. However, current treatment methods are not always effective in preventing the recurrence of ovarian cancer. As a result, the treatments administered after a relapse need to be more aggressive, leading to increased toxicity and drug resistance. To address this issue, researchers are exploring the potential of combining existing anticancer agents with novel or repurposed drugs to reduce the side effects and improve the effectiveness of treatment. In this study, we have investigated the use of rosiglitazone, a well-known anti-diabetic drug, in combination with the chemotherapeutic drug, paclitaxel for the prevention of ovarian cancer. The study utilized the SKOV-3 ovarian cancer cell line to assess the effects of this combination treatment. The results of the study showed that the combination of paclitaxel with rosiglitazone inhibited cell proliferation at much lower concentrations of paclitaxel as compared to paclitaxel alone. The combined treatment also induced cell cycle arrest at the G2/M phase and increased apoptosis by altering the mitochondrial membrane potential of the cells. Additionally, the combination treatment activated the PPAR-γ pathway and downregulated expression of genes associated with cancer stemness, such as NANOG, OCT4, and EHF. Furthermore, the CAM assay substantiated the anti-angiogenic potential of the synergistic treatment of paclitaxel and rosiglitazone. The findings of the study suggest that repurposing rosiglitazone as an anticancer agent in combination with paclitaxel has immense potential to target cancer cell cycle progression and apoptosis, making it a promising therapeutic approach for sensitizing chemo-resistant population of ovarian cancer cells.

Keywords: Anticancer; Ovarian cancer; Paclitaxel; Rosiglitazone; SKOV-3; Synergism.

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Apoptosis* / drug effects
  • Cell Line, Tumor
  • Cell Proliferation* / drug effects
  • Drug Synergism*
  • Female
  • Humans
  • Membrane Potential, Mitochondrial / drug effects
  • Ovarian Neoplasms* / drug therapy
  • Ovarian Neoplasms* / pathology
  • PPAR gamma / metabolism
  • Paclitaxel* / pharmacology
  • Rosiglitazone* / pharmacology

Substances

  • Rosiglitazone
  • Paclitaxel
  • PPAR gamma