NSC 74859 enhances doxorubicin cytotoxicity via inhibition of epithelial–mesenchymal transition in hepatocellular carcinoma cells》.pdf

Cancer Letters 325 (2012) 207–213 Contents lists available at SciVerse ScienceDirect Cancer Letters journal homepage: www.else /locate/canlet NSC 74859 enhances doxorubicin cytotoxicity via inhibition of epithelial–mesenchymal transition in hepatocellular carcinoma cells Qi-Da Hu a,1, Wei Chen a,1, Tian-Lian Yan b, Tao Ma a, Cong-Lin Chen a, Chao Liang a, Qi Zhang a, Xue-Feng Xia a, Hao Liu a, Xiao Zhi a, Xiao-Xiao Zheng a, Xue-Li Bai a, Xia-Zhen Yu a, Ting-Bo Liang a,⇑ a Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China b Department of Gastroenterology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China a r t i c l e i n f o a b s t r a c t Article history: Doxorubicin-based therapy is not effective for the treatment of hepatocellular carcinomas (HCCs), which Received 3 April 2012 often undergo epithelial–mesenchymal transition (EMT) during tumor progression. Activation of signal Received in revised form 6 June 2012 transducer and activator of transcription 3 (STAT3) is associated with chemosensitivity and may contrib- Accepted 2 July 2012 ute to EMT during HCC chemotherapy. Low doses of NSC 78459 (a novel STAT3 inhibitor) have little effect on HCC cell proliferation, but efficiently inhibit STAT3. HuH-7, Hep3B, and HepG2 cells, with epithelial phenotypes, show significantly enhan