Mevalonate Pathway Inhibitor GGTi Limits Pancreatic Cancer Cell Proliferation, while Enhancing Normal Endothelial Cell Function

Overview

An estimated 95,389 people are living with pancreatic cancer in the United States. Chemotherapy and radiation therapy are major treatment modalities for pancreatic cancer, but both can cause severe detrimental side effects in the normal tissue that signifi cantly lower patients’ quality of life. Mevalonate pathway inhibitors have notably been implicated in the treatment of cardiovascular disease but have more recently garnered interest as potential anticancer agents with minimal side effects. PANC -1 cancer c ells were treated with 0, 2, 5, and 10 μM concentrations of GGTi, and proliferation rate was checked using MTT assay. HUVECs were treated with GGTi and generation of activated protein C (APC) was measured by APC generation assay. Finally, radiation sensiti vity of PANC -1 cells, following GGTi treatment, was determined by MTT assay. It was observed that GGTi, dose -dependently, attenuated PANC -1 cell proliferation. It was also observed that GGTi significantly enhanced APC generation in HUVECs. Finally, GGTi further enhanced the radiosensitivity of PANC-1 cancer cells. Here, this study reports for the first time that mevalonate pathway inhibitors, specifically geranylgeranyl transferase inhibitor -2133 (GGTi), attenuates pancreatic cancer cell proliferation and e nhances radiation efficacy, while augmenting physiological function of endothelial cells. Therapeutically, this indicates that GGTi enhances radio - sensitizing effects in pancreatic cancer cells while also exerting vasculoprotective effects. Therefore, the use of GGTi is a novel treatment strategy for future pancreatic cancer patients.

Competition history

• JSHS 2024 Category not listed

Resources

• National JSHS abstract book ↗

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