Basic Research - Cancer(구연) (NP-005) 인간 방광암 세포주에서 MutT homolog (MTH)1 inhibitors의 항암 효과 동국대학교 의과대학 비뇨기과학교실³, 서울대학교 의과대학 비뇨기과학교실 분당서울대학교병원¹, 서울대학교병원² 이정우³,호진녕¹,이상철¹,변석수¹,이은식² Purpose: We investigated the antitumor effects and its possible molecular mechanisms of MutT homolog (MTH)1 inhibitors in cisplatin-sensitive (T24) and resistant (T24R2) human bladder cancer cell lines. Materials and Methods: T24 and T24R2 cells were exposed to MTH1 inhibitors (TH588 or TH287). Tumor cell proliferation was assessed using Cell Counting Kit-8 and clonogenic assays. Flow cytometry was performed to estimate the change in cell cycle and apoptosis. Protein expression related to apoptosis and cell cycle was determined by Western blot. Results: The Cell Counting Kit-8 and clonogenic assays demonstrated the antitumor effects of TH588 alone or TH287 alone on T24 and T24R2 cells in a dose dependent manner. A flow cytometric analysis showed cell cycle arrest at the G2/M phase after the treatment of TH588 or TH287 for 24 hours in T24 and T24R2 cells. TH588 or TH287 induced apoptosis via increased expression of PARP, caspase-3, 8, and 9, and cytochrome c. Cell cycle arrest induced by TH588 or TH287 was accompanied by increased expression of cyclin B1. Conclusions: Results reveal that MTH1 inhibitors have potent antitumor effects in cisplatin-sensitive and resistant bladder cancer cells. These findings suggest MTH1 inhibitor as an attractive novel class of chemotherapeutic agents in patients not only with advanced bladder cancer but also who are refractory or recur to first-line cisplatin-based chemotherapy. keywords : bladder cancer, MutT homolog 1, antitumor effect