Silencing of APE1 enhances sensitivity of human hepatocellular carcinoma cells to radiotherapy in vitro and in a xenograft model

• Published in: PloS one 2013-02, Vol.8 (2), p.e55313-e55313
• Main Authors: Cun, Yanping, Dai, Nan, Xiong, Chengjie, Li, Mengxia, Sui, Jiangdong, Qian, Chengyuan, Li, Zheng, Wang, Dong
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; Apoptosis - genetics; Apoptosis - radiation effects; Biology; Biotechnology; Bone cancer; Cancer therapies; Carcinoma, Hepatocellular - genetics; Carcinoma, Hepatocellular - radiotherapy; Cell cycle; Cell growth; Cell Line, Tumor; Colorectal cancer; Deoxyribonucleic acid; DNA; DNA binding proteins; DNA damage; DNA repair; DNA-(Apurinic or Apyrimidinic Site) Lyase - genetics; DNA-(Apurinic or Apyrimidinic Site) Lyase - metabolism; Dose-Response Relationship, Radiation; Down-Regulation; Endonuclease; Enzymes; Gene expression; Gene regulation; Gene Silencing - physiology; Growth inhibition; Hepatocellular carcinoma; Humans; Inhibition; Ionizing radiation; Irradiation; Liver cancer; Liver Neoplasms - genetics; Liver Neoplasms - radiotherapy; Medicine; Mice; Multiple myeloma; Neoplasm Transplantation; p53 Protein; Proteins; Radiation dosage; Radiation therapy; Radiation Tolerance; Radioresistance; Radiosensitivity; Radiotherapy; RNA, Small Interfering; Rodents; Sensitivity; Sensitivity enhancement; siRNA; Studies; Surgery; Transcription (Genetics); Transcription factors; Transplantation, Heterologous; Tumor proteins; Tumors; Xenografts
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0055313

Resistance to radiotherapy is a key limitation for the treatment of human hepatocellular carcinoma (HCC). To overcome this problem, we investigated the correlation between radioresistance and the human apurinic/apyrimidinic endonuclease (APE1), a bifunctional protein, which plays an important role in DNA repair and redox regulation activity of transcription factors. In the present study, we examined the radiosensitivity profiles of three human HCC cell lines, HepG2, Hep3B, and MHCC97L, using the adenoviral vector Ad5/F35-mediated APE1 siRNA (Ad5/F35-siAPE1). The p53 mutant cell lines MHCC97L showed radioresistance, compared with HepG2 and Hep3B cells. APE1 was strongly expressed in MHCC97L cells and was induced by irradiation in a dose-dependent manner, and Ad5/F35-siAPE1 effectively inhibited irradiation-induced APE1 and p53 expression. Moreover, silencing of APE1 significantly potentiated the growth inhibition and apoptosis induction by irradiation in all tested human HCC cell lines. In addition, Ad5/F35-siAPE1 significantly enhanced inhibition of tumor growth and potentiated cell apoptosis by irradiation both in HepG2 and MHCC97L xenografts. In conclusion, down regulation of APE1 could enhance sensitivity of human HCC cells to radiotherapy in vitro and in vivo.