RT Journal Article
SR Electronic
T1 Inhibition of Signal Transducer and Activator of Transcription 3 and Cyclooxygenase-2 Is Involved in Radiosensitization of Cepharanthine in HeLa Cells
JF International Journal of Gynecologic Cancer
JO Int J Gynecol Cancer
FD BMJ Publishing Group Ltd
SP 608
OP 614
DO 10.1097/IGC.0b013e31828a05fd
VO 23
IS 4
A1 Zhen-hao Fang
A1 Yan-jing Li
A1 Zan Chen
A1 Jun-jie Wang
A1 Li-hong Zhu
YR 2013
UL http://ijgc.bmj.com/content/23/4/608.abstract
AB Objectives To investigate the radiosensitizing effects of cepharanthine (CEP) in the human cervical adenocarcinoma HeLa cell line and to examine the underlying mechanisms.Materials/Methods Survival of HeLa cells after treatment with or without ionizing radiation (IR) and CEP administration was investigated. MTT assays and apoptosis analysis were used to assess cytotoxicity. Nude mouse xenografts were established to evaluate the antitumor effects of CEP and IR in vivo. Expression of signal transducer and activator of transcription 3 (STAT3) and its downstream signaling molecules as well as cyclooxygenase-2 (COX-2) were examined by Western blot analysis.Results Clonogenic assays showed that treatment with CEP and IR resulted in significant radiosensitization. Cepharanthine and IR treatment achieved maximum cytotoxic effects on HeLa cells with regard to apoptosis induction. Cepharanthine efficiently decreased IR-induced STAT3 and COX-2 activation. The STAT3 target genes, including the antiapoptotic Bcl-2 and the cell cycle regulator c-Myc, were decreased concomitantly. In vivo administration of CEP (20 mg/kg every 2 days) combined with radiation in HeLa xenografts enhanced tumor growth delay and apoptosis (indicated by activated caspase-3 Western blot analysis), with reduced expression of STAT3, Bcl-2, c-Myc, and COX-2.Conclusions Cepharanthine was shown to induce radiation sensitization in HeLa cells in vitro and in vivo. The inhibitory effects of CEP on STAT3 signaling pathway and COX-2 help us to better understand the radiosensitization of CEP.