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Sitagliptin Modulates the Response of Ovarian Cancer Cells to Chemotherapeutic Agents

Agnieszka Kosowska1, Wojciech Garczorz1, Agnieszka Kłych-Ratuszny1

  • 1Department of Biochemistry, Faculty of Medical Sciences in Katowice, Medical University of Silesia, Medyków 18, 40-752 Katowice, Poland.

International Journal of Molecular Sciences
|December 1, 2020
PubMed

Insights

Sitagliptin, a diabetes drug, enhances chemotherapy by inducing apoptosis and reducing ovarian cancer cell migration. Combined with paclitaxel, it modulates signaling pathways, potentially improving treatment response.

Area of Science:

  • Oncology
  • Endocrinology
  • Pharmacology

Background:

  • Type 2 diabetes mellitus and cancer share a strong association, with increasing global incidence.
  • Anti-diabetic medications, including DPP-4 inhibitors like sitagliptin, are being investigated for their impact on cancer.
  • Ovarian cancer remains a significant health concern, necessitating novel therapeutic strategies.

Purpose of the Study:

  • To investigate the effects of sitagliptin, alone and with paclitaxel, on epithelial ovarian cancer cell development and metastasis.
  • To analyze sitagliptin's influence on apoptosis, migration, invasiveness, and metalloproteinase (MMP) and tissue inhibitor of metalloproteinase (TIMP) production in ovarian cancer cells.

Main Methods:

  • Utilized two human ovarian cancer cell lines (SKOV-3 and OVCAR-3).
  • Assessed cell migration, invasiveness, and apoptosis (caspase 3/7 activation).
  • Quantified MMP and TIMP production and analyzed ERK and Akt signaling pathways.

Main Results:

  • Sitagliptin induced apoptosis in paclitaxel-treated ovarian cancer cells.
  • Sitagliptin maintained paclitaxel's effects on ERK and Akt signaling.
  • Sitagliptin reduced migration and invasiveness in SKOV-3 cells and altered MMP/TIMP profiles.

Conclusions:

  • Sitagliptin combined with paclitaxel may offer a strategy for pharmacological modulation of intracellular pathways.
  • This combination could potentially improve chemotherapy response in ovarian cancer treatment.
  • Sitagliptin demonstrates potential as an adjunct therapy in ovarian cancer, warranting further investigation.
Keywords:
apoptosisdiabetesmetalloproteinasesmetastasisovarian cancersitagliptin

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