RESEARCH ARTICLE MicroRNA-200a/b influenced the therapeutic effects of curcumin in hepatocellular carcinoma (HCC) cells Hung-Hua Liang & Po-Li Wei & Chin-Sheng Hung & Chun-Te Wu & Weu Wang & Ming-Te Huang & Yu-Jia Chang Received: 12 March 2013 / Accepted: 27 May 2013 # International Society of Oncology and BioMarkers (ISOBM) 2013 Abstract MicroRNAs (miRNAs) play an essential role in regulating gene expression in normal and malignant cells. Expression of the microRNA-200 (miR-200) family has been correlated with malignancy in cancers. However, whether miR-200a/b plays a role in curcumin-mediated treat- ment of hepatocellular carcinoma (HCC) is unknown. We performed miRNA array analyses in two different HCC cell lines (HepG2 and HepJ5). The expression patterns of miR- 200 family members were assessed with real-time PCR. We overexpressed miR-200 family members using a lentiviral system and selected stably transduced clones with antibi- otics. The anticancer effects of curcumin on J5-200a, J5- 200b, and J5-control cells were assessed by MTT assay, flow cytometry cell cycle analysis, and TUNEL assay. We found that HepG2 cells, which were more resistant to curcumin treatment than HepJ5 cells, expressed higher levels of miR- 200a/b. The MTT assay revealed that the overexpression of miR-200a/b in HepJ5 cells conferred enhanced resistance to curcumin treatment compared with the control cells. By cell cycle analysis and TUNEL assay, we found that apoptosis was increased dramatically in J5-control cells compared with J5-200a and J5-200b cells after curcumin treatment. Finally, we evaluated the levels of Bcl-2, Bax, and Bad, and found a decrease of Bcl-2 levels and increase of Bad levels in the J5- control cells treated with curcumin. The expression levels of miR-200a/b might determine the therapeutic efficacy of curcumin on HCC cells. Keywords miR-200 . HCC . Anti-proliferative . Curcumin Abbreviations miR-200 MicroRNA-200 HCC Hepatocellular carcinoma Introduction Hepatocellular carcinoma (HCC) is the fifth most common malignancy worldwide, with a relatively high incidence in Asia [1]. Despite the rapid progress in anticancer therapeutics, H.<H. Liang : P.<L. Wei : C.<S. Hung : M.<T. Huang : Y.<J. Chang Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan H.<H. Liang : P.<L. Wei : C.<S. Hung : W. Wang : M.<T. Huang : Y.<J. Chang Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan H.<H. Liang : P.<L. Wei : C.<S. Hung : W. Wang : M.<T. Huang : Y.<J. Chang Division of General Surgery, Department of Surgery, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan H.<H. Liang : P.<L. Wei : C.<S. Hung : Y.<J. Chang Cancer Research Center, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan P.<L. Wei : Y.<J. Chang (*) Center of Excellence for Cancer Research, Taipei Medical University, 250 Wu-Xin Street, Taipei City, Taiwan 110 e-mail: r5424012@tmu.edu.tw M.<T. Huang (*) Division of General Surgery, Department of Surgery, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan e-mail: mthuant@tmu.edu.tw C.<T. Wu Chang Gung University College of Medicine and Chang Gung Institute of Technology, Taipei, Taiwan C.<T. Wu Department of Urology, Chang Gung Memorial Hospital at Keelung, Keelung, Taiwan Tumor Biol. DOI 10.1007/s13277-013-0891-z