A549 폐 선암종 세포와 HT-29 결장암 세포 성장 기전에서 NF-κB 세포신호전달에 대한 인간 지방조직유래 중간엽 줄기세포의 이중효과에 관한 연구

학위논문 (석사)-- 서울대학교 대학원 : 의학과, 2014. 2. 강병철.Human adipose tissue-derived mesenchymal stem cells (hATMSCs) have a great potential as therapy for various diseases and in regenerative medicine. However, emerging evidence suggests that human stem cells have both promoting and inhibitory effects on tumor growth. For the clinical use of hATMSCs as a novel cell therapy, it is important to determine in which tumor environments hATMSCs have tumor supporting effects or suppressing effects and to understand the underlying mechanisms. In this study, hATMSCs affected tumor growth differently depending on the types of tumor cell. Among several types of tumor cell lines, the hATMSCs particularly inhibited the growth of A549 lung adenocarcinoma cells, but promoted the growth of HT-29 colon cancer cells in an in vivo xenograft model. Additional results from an in vitro study were coincided with the in vivo experiment of hATMSCs effects on tumor growth in A549 and HT-29 cell lines. The hATMSCs induced apoptosis and inhibited proliferation of A549 lung cancer cells, but the hATMSCs conversely affected the HT-29 colon cancer cells. Also, the change in NF-κB expression level after hATMSC treatment was the same in both the in vivo and in vitro experiments. The expression level of phosphorylated NF-κB p65 was reduced in A549 tumor cells, but the level was increased in HT-29 tumor cells. Altogether, we demonstrated dual effects of hATMSCs, which included an inhibiting effect on A549 and a promoting effect on HT-29. The expression level of NF-κB p65 was correlated with these dual effects in the A549 and HT-29 tumor cell lines.ABSTRACT CONTENTS LIST OF FIGURES LIST OF ABBREVIATIONS INTRODUCTIONS MATERIALS AND METHODS Tumor cell lines Isolation and culture of hATMSCs In vivo tumor xenograft model In vitro coculture and trypan blue exclusion assay Western blot analysis Histopathological analysis Flow cytometry analysis Statistical analysis RESULTS Immunophenotype of hATMSCs The effect of hATMSCs on the growth of various types of tumors in an in vivo xenograft model Molecular changes of phosphorylated NF-κB p65 in A549 and HT-29 tumors induced by the hATMSCs treatment Histopathological changes in A549 and HT-29 tumors following hATMSCs treatment The effect of hATMSCs on the cell viability of tumor cell lines, A549 and HT-29 in vitro The coculture effect of hATMSCs on the tumor cell apoptosis and proliferation The coculture effect of hATMSCs on the phosphorylated NF-κBp65 expression in A549 and HT-29 tumor cell lines DISCUSSION REFERENCES ABSTRACT IN KOREAN (국문초록)Maste