Basic Research - Cancer(구연) Oral Session 3 / Basic Research - Cancer (Ⅱ) (O-032) Rm.201 10월 30일(수) 14:00-15:00 Bacillus calmette-guerin cell wall cytoskeleton with encapsulated liposome enhances antitumor effect in bladder cancer through inhibition of mTOR activity and induction of reactive oxygen species ¹중앙대학교 의과대학 비뇨기과학교실, ²약학대학 황영미¹, 윤다현¹, 황광용¹, 윤호엽², 최영욱², 장인호¹ Objective: The Mycobacterium bovis Bacille Calmette–Guerin cell wall skeleton (BCG-CWS), the main immune active center of BCG, is a potent candidate as a non-infectious immunotherapeutic drug instead of live BCG against urothelial carcinoma (URCa). However, the most limited application for anticancer therapy, it is difficult to formulate a water-soluble BCG-CWS due to the aggregation of BCG-CWS in both aqueous and non-aqueous solvents. Materials and methods: Here, to improve the internalization of BCG-CWS into bladder cancer cells, we developed 180 nm-sized lipid particles of BCG-CWS in methylene chloride solvent (BCG-CWS-CL). Results: Treatment of BCG-CWS-CL was more effective in growth inhibition of URCa cells in vitro and orthotopic bladder cancer mouse model in vivo than nonenveloped BCG-CWS. Treatment of BCG-CWS-CL induced the inhibition of mTOR activation and cleaved PARP (marker of apoptosis) in URCa cells. The blockade of mTOR activity following BCG-CWS-CL treatment resulted in induction of autophagy-related proteins in URCa cells. BCG-CWS-CL mediated cell death was mediated predominantly by the generation of reactive oxygen species (ROS). Conclusions: Therefore, our data suggest that encapsulated BCG-CWS into nanoparticles using the liposome can permit facilitating cellular endocytosis of active center of BCG in bladder cancer and providing a promising therapeutic strategy for enhancing BCG therapy. The National Research Foundation (NRF) of the Republic of Korea (NRF-2016R1D1A1B03933826 to Y.M.W., NRF-2018R1D1A1A02050248 to I.H.C.) and the Korea Health Technology R&D Project (HI17C0710 to I.H.C.). keywords : Bacillus calmette-guerin cell wall cytoskeleton, bladder cancer, mTOR