Park Geumi, Baniya Manoj Kumar, Cha Eun-Jeong, Sim So Jin, Choi Joon-Seok, Chun Kyung-Soo
College of Pharmacy, Keimyung University, Daegu, Korea.
Preclinical Research Center, Daegu-Gyeongbuk Medical Innovation Foundation (K-MEDIhub), Daegu, Korea.
J Cancer Prev. 2025 Mar 30;30(1):24-31. doi: 10.15430/JCP.24.032.
Renal cancer continues to offer a great challenge for its successful therapy today, thus underscoring the need for effective chemotherapeutic agents. In the current study, we explored the anticancer effects of domperidone, a dopamine D2 receptor (DRD2) antagonist, in renal cancer Caki-2 cells. Domperidone induced dose and time-dependent cytotoxic effects in Caki-2 cells, triggering intrinsic apoptosis via the stimulation of the caspase cascade and PARP cleavage. The cytotoxic effect of domperidone was found to be partially DRD2-dependent. Domperidone treatment markedly augmented the production of intracellular reactive oxygen species which induced the cell death of Caki-2 cells. In addition, domperidone suppressed Janus kinase 2 and STAT3 phosphorylation, leading to inhibition of survival and proliferation of these cells. Hence, domperidone can be considered a promising candidate for renal cancer treatment.
如今，肾癌的成功治疗仍然面临巨大挑战，这凸显了对有效化疗药物的需求。在本研究中，我们探究了多巴胺D2受体（DRD2）拮抗剂多潘立酮对肾癌Caki-2细胞的抗癌作用。多潘立酮在Caki-2细胞中诱导剂量和时间依赖性的细胞毒性作用，通过刺激半胱天冬酶级联反应和PARP裂解引发内源性凋亡。发现多潘立酮的细胞毒性作用部分依赖于DRD2。多潘立酮处理显著增加了细胞内活性氧的产生，从而诱导Caki-2细胞死亡。此外，多潘立酮抑制了Janus激酶2和STAT3的磷酸化，导致这些细胞的存活和增殖受到抑制。因此，多潘立酮可被视为肾癌治疗的一个有前景的候选药物。
