title: Interferon-α2b gene-modified human bone marrow mesenchymal stem cells inhibit hepatocellular carcinoma by reducing the Notch1 levels.
abstract: OBJECTIVE
  Hepatocellular carcinoma (HCC) is the most common liver cancer worldwide. IFN-α has been used in clinics as a potential therapeutic strategy to treat HCC. In spite of the therapeutic effects, IFN-α caused many side effects due to its short half-life and high dose. Here, we aim to detect the anti-tumor effect of a novel gene delivery system - IFN-α2b gene-modified human bone marrow mesenchymal stem cells (BMSCs) in HCC.
  
  
  METHODS
  Two HCC cell lines, HepG2 and Huh7 were used in the current study. The secretion of IFN-α2b in the BMSC cultured conditioned media (CM) was measured by ELISA. The cell cycle was determined by flow cytometry. The Xenografted NOD/SCID mouse tumor model was generated by subcutaneous inoculation with HepG2 cells.
  
  
  RESULTS
  We found that the IFN-α2b-modified BMSC (BMSC/IFN-α2b) could express IFN-α2b stably. The CM from BMSC/IFN-α2b inhibited the proliferation of HCC cells with a much lower growth rate compared with BMSC/vector-CM or DMEM culture group. We further demonstrated that the population of G2/M phase was higher in BMSC/IFN-α2b-CM treated cells than the other two groups. In addition, BMSC/IFN-α2b could significantly inhibit tumor growth in NOD/SCID mice. Moreover, we found that BMSC/IFN-α2b-CM could significantly decrease the mRNA and protein levels of Notch signaling molecules of HCC in vitro and in vivo.
  
  
  CONCLUSIONS
  Our data demonstrated that BMSC/IFN-α2b could significantly inhibit HCC cell growth through negatively regulating the Notch signaling, which suggested that IFN-α2b-modified BMSC may be used as an effective therapeutic strategy for hepatomas.
authors.affiliation: Department of general surgery, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, China.
authors.forename: Yanjun
authors.initials: Y
authors.lastname: Su
authors.affiliation: Department of general surgery, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, China.
authors.forename: Ruochuan
authors.initials: R
authors.lastname: Cheng
authors.affiliation: Department of general surgery, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, China.
authors.forename: Jianming
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of general surgery, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Qian
authors.affiliation: Department of general surgery, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, China.
authors.forename: Chang
authors.initials: C
authors.lastname: Diao
authors.affiliation: Department of Hepatobiliary Surgery, The Calmette Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650011, China.
authors.forename: Jianghua
authors.initials: J
authors.lastname: Ran
authors.affiliation: Department of Hepatobiliary Surgery, The Calmette Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650011, China.
authors.forename: Hongqing
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Hepatobiliary Surgery, The Calmette Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650011, China. Electronic address: lilibio@126.com.
authors.forename: Li
authors.initials: L
authors.lastname: Li
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000628:therapy*; D018014:Gene Transfer Techniques; D056945:Hep G2 Cells; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage / Q000235:genetics*; D008113:Liver Neoplasms / Q000235:genetics* / Q000628:therapy*; D008297:Male; D059630:Mesenchymal Stem Cells; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D051881:Receptor, Notch1 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D023041:Xenograft Model Antitumor Assays / Q000379:methods
chemical_list: D016898:Interferon-alpha; C497762:Notch1 protein, mouse; D051881:Receptor, Notch1
keywords: Bone marrow mesenchymal stem cells; Hepatoma; IFN-α2b; Notch signaling pathway