| Autor: |
Lee SY; Department of Physiology, School of Medicine, Pusan National University, Yangsan 50612, Gyeongsangnam-do, Republic of Korea., Shin MJ; Department of Physiology, School of Medicine, Pusan National University, Yangsan 50612, Gyeongsangnam-do, Republic of Korea., Choi SM; Department of Physiology, School of Medicine, Pusan National University, Yangsan 50612, Gyeongsangnam-do, Republic of Korea., Kim DK; HiCellTech Inc., Yangsan 50612, Gyeongsangnam-do, Republic of Korea., Choi MG; Department of Physiology, School of Medicine, Pusan National University, Yangsan 50612, Gyeongsangnam-do, Republic of Korea., Kim JS; Department of Physiology, School of Medicine, Pusan National University, Yangsan 50612, Gyeongsangnam-do, Republic of Korea., Suh DS; Department of Obstetrics and Gynecology, School of Medicine, Pusan National University, Yangsan 50612, Gyeongsangnam-do, Republic of Korea., Kim JH; Department of Physiology, School of Medicine, Pusan National University, Yangsan 50612, Gyeongsangnam-do, Republic of Korea., Kim SJ; Department of Nuclear Medicine, School of Medicine, Pusan National University, Yangsan 50612, Gyeongsangnam-do, Republic of Korea. |
| Abstrakt: |
Peroxisome proliferator-activated receptors (PPARs), including PPAR-α, PPAR-β/δ, and PPAR-γ, are involved in various cellular responses, including metabolism and cell proliferation. Increasing evidence suggests that PPARs are closely associated with tumorigenesis and metastasis. However, the exact role of PPARs in energy metabolism and cancer stem cell (CSC) proliferation remains unclear. This study investigated the role of PPARs in energy metabolism and tumorigenesis in ovarian CSCs. The expression of PPARs and fatty acid consumption as an energy source increased in spheroids derived from A2780 ovarian cancer cells (A2780-SP) compared with their parental cells. GW6471, a PPARα inhibitor, induced apoptosis in A2780-SP. PPARα silencing mediated by small hairpin RNA reduced A2780-SP cell proliferation. Treatment with GW6471 significantly inhibited the respiratory oxygen consumption of A2780-SP cells, with reduced dependency on fatty acids, glucose, and glutamine. In a xenograft tumor transplantation mouse model, intraperitoneal injection of GW6471 inhibited in vivo tumor growth of A2780-SP cells. These results suggest that PPARα plays a vital role in regulating the proliferation and energy metabolism of CSCs by altering mitochondrial activity and that it offers a promising therapeutic target to eradicate CSCs. |
