title: Silencing of APE1 enhances sensitivity of human hepatocellular carcinoma cells to radiotherapy in vitro and in a xenograft model.
abstract: 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.
authors: Cancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing, People's Republic of China.
authors: Yanping
authors: Y
authors: Cun
authors: Nan
authors: N
authors: Dai
authors: Chengjie
authors: C
authors: Xiong
authors: Mengxia
authors: M
authors: Li
authors: Jiangdong
authors: J
authors: Sui
authors: Chengyuan
authors: C
authors: Qian
authors: Zheng
authors: Z
authors: Li
authors: Dong
authors: D
authors: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000528:radiation effects; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000532:radiotherapy; D045744:Cell Line, Tumor; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000235:genetics* / Q000378:metabolism; D004307:Dose-Response Relationship, Radiation; D015536:Down-Regulation; D020868:Gene Silencing / Q000502:physiology*; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000532:radiotherapy; D051379:Mice; D009368:Neoplasm Transplantation; D034741:RNA, Small Interfering; D011836:Radiation Tolerance; D014183:Transplantation, Heterologous
chemical_list: D034741:RNA, Small Interfering; C085108:APEX1 protein, human; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase