S-Space College of Medicine/School of Medicine (의과대학/대학원) Dept. of Medicine (의학과) Theses (Ph.D. / Sc.D._의학과)
The Inhibitory Effect of Nicotinamide on Human Intrahepatic Cholangiocarcinoma Cells
인체 담관암세포에서 니코틴아마이드(NA)의 종양 억제 효과
- 의과대학 의학과
- Issue Date
- 서울대학교 대학원
- 학위논문 (박사)-- 서울대학교 대학원 : 의학과, 2017. 2. 장자준.
- Background: Intrahepatic cholangiocarcinoma (iCCA) is a devastating malignancy with no effective treatment
it is associated with a high mortality rate. Nicotinamide (NA, the amide form of vitamin B3) has been shown to be effective in the treatment of various diseases. However, the effects of NA in iCCA have not been studied.
Materials and Methods: Four human iCCA cell lines (HuCCT1, JCK, OZ and Cho-CK) were used to test the inhibitory effect of NA. Cell proliferation was assessed by WST1 and BrdU assays, cell cycle was evaluated by flow cytometry using propidium iodide, apoptosis was detected by Annexin V-FICT assay and the invasive potential of iCCA cells was tested by invasion assay. Western blotting was used to detect the changes at protein level. Besides, the p53 specific siRNA was used to knockdown the p53 expression in iCCA.
Results: NA significantly inhibited cell viability and induced apoptosis in all four cell lines. It arrested cell cycle in G1 phase, decreased Cyclin D1 and Cdk4 protein expression levels and increased p16 level. NA increased the levels of cleaved caspases 3 and 9, but had no effect on caspase 8. In HuCCT1 and OZ cell lines, NA treatment significantly impaired the invasion abilities and inhibited epithelial-mesenchymal transition (EMT)-like changes, such as increase in epithelial marker E-cadherin expression, decrease in mesenchymal marker vimentin and EMT transcription factors Slug expression.
Conclusions: We showed for the first time that NA markedly inhibited cell proliferation, induced apoptosis and attenuated invasiveness in human iCCA. Our findings provide the experimental basis for using NA as a potential anticancer agent against human iCCA in the future.