Basic Research - Cancer(구연) Oral Session1 / Basic Research - Cancer (Ⅰ) (O-011) Rm.201 10월 30일(수) 13:00-14:00 Inhibition of tumor growth using TRAIL overexpressing adipose derived stem cell is enhanced by combination with chemotherapeutic agent CPT-11 in castration resistant prostate cancer 순천향대학교 의과대학 비뇨기과학교실, ¹순천향대학교병원 임상의학연구소 송윤섭, 오은정, 한지윤, 이현영, 김재헌, 두승환, 양원재, 한용석¹, 이상훈¹ Purpose: As TRAIL induces apoptosis selectively in tumor cells, it an excellent candidate therapeutic for treating cancer patients. Stem cells overexpressing TRAIL gene have been recognized as an attractive tool for treating CRPC. Chemotherapeutic agent CPT-11 was shown to augment TRAIL induced apoptosis in prostate cancer tumors. This study was performed to investigate the inhibition of tumor gowth using TRAIL overexpressing adipose stem cell is enhanced by combination with chemotherapeutic agent CPT-11 in CRPC bearing mice. Materials and Methods: hERT-ADSC.sTRAIL cell line was established by transfection with a lentiviral vector (CLV-Ubic) encoding human sTRAIL gene. qPCR and western blot to confirm genes over-expression were performed. Invasion study for the selective migration ability toward PC3 cells was performed. To determine the antitumor effect of ADSC.sTRAIL combined with CPT-11, PC3 cells were co-cultured with hERT-ADSC.sTRAIL under the concentrations of CPT-11 (5μM). PC3 cells (1x106 cells) were injected subcutaneously into the flank of nude mice. At 2 days after intracardiac injection of ADSC.sTRAIL cells, animals were treated with CPT-11 for 4 weeks. Tumor volumes were measured. Result: Therapeutic sTRAIL genes were successfully delivered to human ADSC. In vitro study, viability of PC3 cells significantly decreased in the presence of ADSC.sTRAIL (62.7±2.0) under CPT-11 compared with ADSC under CPT-11 (76.2±3.8), CPT-11(83.0±1.0) at the ratio as low as 0.05 (PC3: ADSC.sTRAIL) (p<0.05). Percentage of Annexin V–positive apoptotic PC3 cells significantly increased in the presence of ADSC. sTRAIL (37.2±2.1) under CPT-11 compared with ADSC under CPT-11 (23.8±3.8), CPT-11 alone (16.5± 1.0) (p<0.05). In vivo study, tumor volume percent of ADSC. sTRAIL treatment under CPT-11 (89.6±4.6) were reduced, compared with ADSC under CPT-11 (101.0±3.8), CPT-11 alone group (106.8±6.0), no treatment group (1287.8±35.5) (p<0.05). ADSC.sTRAIL in combination with CPT-11 inhibited the growth of tumor up to 17.2% compared with CPT-11 alone. Conclusion: Inhibition of tumor gowth using ADSC.sTRAIL was enhanced by combination with CPT-11 in CRPC bearing mice. These results indicate that ADSC expressing sTRAIL genes combined CPT-11 can provide a new strategy for treating CRPC in clinical trials using patient patient’s own ADSC. keywords : Prostate cancer, TRAIL, CPT-11