The Impact of the Antidiabetic Agent Sitagliptin on the Radiation Response of Breast Carcinoma Cells with Different Metastatic Capacities.
Eling Marie Theres MT, Bottema Anouk A, Savic Dragana D, Skvortsov Sergej S et al.
Breast cancer (BC) and type 2 diabetes mellitus (T2DM) often co-occur and can contribute to poorer clinical outcomes after therapy compared to non-diabetic cases. It is assumed that glucose-lowering drugs like DPP4 inhibitors (DPP4-Is), e.g., sitagliptin, can affect the radiation responses of BC cells. In this study, parental and invasive (INV) MDA-MB-231 (triple-negative BC) and T47D (luminal A) cells were used. INV cells revealed a significant upregulation of DPP4/CD26 molecules compared to their parental counterparts. All investigated cells were treated with sitagliptin, ionizing radiation, or both. It was found that the specific inhibition of DPP4/CD26 molecules using sitagliptin can protect triple-negative BC cells from cytotoxic ionizing radiation or improve the radiation response in luminal A BC cells independently of their metastatic abilities. The protective and sensitizing effects of sitagliptin do not depend on the level of senescence and/or autophagy initiation after treatment.