Polo-like kinase 1 inhibitor NMS-P937 represses nasopharyngeal carcinoma progression via induction of mitotic abnormalities.

Abstract

Polo-like kinase 1 (PLK1) inhibitor NMS-P937 is a targeted therapeutic agent with good preclinical efficacy in various human cancers, and its therapeutic effect on nasopharyngeal carcinoma (NPC) remains to be determined. Here, to explore biological activity of NMS-P937 in NPC, multiple types of NPC cells were utilized. We tested IC50 values, carried out flow cytometry, western blot analysis analysis, immunofluorescence, and constructed subcutaneous xenograft mouse models. We found that treatment with NMS-P937 increased the proportion of G2/M phase NPC cells, where CyclinB1 expression was upregulated and CyclinE1 expression was downregulated. Besides, NMS-P937 treatment-induced NPC cell apoptosis with increased cleavage of PARP and caspase-3. Mechanistically, NMS-P937 treatment led to aberrant mitosis, causing increased reactive oxygen species (ROS) levels. ROS scavenger N-acetylcysteine partially reversed ROS levels induced by NMS-P937. Furthermore, NMS-P937 administration restrained NPC xenografts growth in nude mice. Overall, NMS-P937 suppressed NPC cell proliferation and increased ROS levels, causing cell cycle abnormalities and apoptosis. NMS-P937 holds great promise as a therapeutic agent for treating nasopharyngeal carcinoma.