Medical Oncology

, Volume 28, Supplement 1, pp 301–309

Slug inhibition upregulates radiation-induced PUMA activity leading to apoptosis in cholangiocarcinomas

  • Kejun Zhang
  • Bingyuan Zhang
  • Yun Lu
  • Chuandong Sun
  • Wei Zhao
  • Xuelong Jiao
  • Jilin Hu
  • Peng Mu
  • Hai Lu
  • Changyong Zhou
Original Paper

Abstract

Resistance of cholangiocarcinoma to irradiation therapy is a major problem in cancer treatment. Slug, a snail family transcription factor, is a suppressor of PUMA (p53 upregulated modulator of apoptosis), which has been shown to be involved in the control of apoptosis. In this study, we investigated whether the modulation of Slug expression, using adeno-associated-virus-mediated transfer of siRNA targeting Slug gene (rAAV2-Slug siRNA), affects cholangiocarcinoma sensitivity to radiation. In the present study, we used rAAV2-Slug siRNA to downregulate the expression of Slug in QBC939 cholangiocarcinoma cell lines in vitro before γ-irradiation. In vivo studies were done with orthotopic cholangiocarcinoma, and radiosensitivity was evaluated both in vitro and in vivo. rAAV2-Slug siRNA transfection resulted in downregulation of the levels of Slug in QBC939 cells. In addition, rAAV2-Slug siRNA, in combination with radiation, increased levels of the PUMA, which contributes to the radiosensitivity of cholangiocarcinomas. Finally, treatment with rAAV2-Slug siRNA plus γ-irradiation completely regressed tumor growth in orthotopic cholangiocarcinomas model. In summary, integrating gene therapy with radiotherapy could have a synergistic effect, thereby improving the survival of patients with cholangiocarcinomas.

Keywords

Snail family transcription factor p53 upregulated modulator of apoptosis Apoptosis Radiation 

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Kejun Zhang
    • 1
  • Bingyuan Zhang
    • 1
  • Yun Lu
    • 1
  • Chuandong Sun
    • 1
  • Wei Zhao
    • 1
  • Xuelong Jiao
    • 1
  • Jilin Hu
    • 1
  • Peng Mu
    • 2
  • Hai Lu
    • 3
  • Changyong Zhou
    • 4
  1. 1.Department of General Surgery, The Affiliated Hospital of Medical CollegeQingDao UniversityQingDaoPeople’s Republic of China
  2. 2.Department of Pathology, The Affiliated Hospital of Medical CollegeQingDao UniversityQingDaoPeople’s Republic of China
  3. 3.Department of Molecular Biology, The Affiliated Hospital of Medical CollegeQingDao UniversityQingDaoPeople’s Republic of China
  4. 4.Department of Emercency Medicine, The Affiliated Hospital of Medical CollegeQingDao UniversityQingDaoPeople’s Republic of China

Personalised recommendations