Reversed Effect of All-trans Retinoic Acid on Enrichment of Liver Cancer Stem Cells by Chemotherapy Drugs
LIU Jing-tao, ZHANG Yan-hua*
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Pharmacy Department, Peking University Cancer Hospital, Beijing 100142, China
Abstract��OBJECTIVE To investigate the relationship between chemotherapy resistance and cancer stem cells, probe the way to reverse drug resistance, and guide the rational medical treatment. METHODS Hepatocellular carcinoma cell lines, parent and chemoresistant HepG-2, were cultured with fluorouracil (5-FU). CCK-8 cell proliferation assay was used to determine the inhibition of 5-Fu and all-trans retinoic acid (ATRA), a cell differentiation inducer. The content difference of cancer stem cells between parent and chemoresistant HepG-2 cell lines was examined by flow cytometry. Western blot and realtime PCR were preformed to probe the difference of related gene expression level between parent and chemoresistant HepG-2 cell lines. RESULTS Our data supported that the inhibitory effect of 5-Fu alone on chemoresistant HepG-2 cells proliferation was lower than on parent HepG-2 cells. After the addition of ATRA, chemoresistant HepG-2 cells proliferation was reduced obviously. Flow cytometry RESULTS revealed that compared with parent HepG-2 cells, the ratio of CD44 and CD326 positive cells in chemoresistant HepG-2 cells was much more than that in parent HepG-2 cells. Furthermore, realtime PCR and Western blot suggested that ABCG2, BMI and OCT4 expressions were increased in chemoresistant HepG-2 cells than those in parent HepG-2 cells, while ATRA could attenuate these differences on protein expressions. CONCLUSION Cancer stem cells enrichment relates to chemotherapy resistance, which can be reversed by ATRA through down-regulation cancer stem cells associated gene expression. This can provide new ideas for clinical rational use of anti-tumor drugs.
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LIU Jing-tao, ZHANG Yan-hua. Reversed Effect of All-trans Retinoic Acid on Enrichment of Liver Cancer Stem Cells by Chemotherapy Drugs. Chinese Pharmaceutical Journal, 2016, 51(24): 2119-2123.
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2016, Vol. 51 
