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Inhibition of Signal Transducer and Activator of Transcription 3 and Cyclooxygenase-2 Is Involved in Radiosensitization of Cepharanthine in HeLa Cells
  1. Zhen-hao Fang, BS,
  2. Yan-jing Li, BS,
  3. Zan Chen, BS,
  4. Jun-jie Wang, MD and
  5. Li-hong Zhu, MD
  1. Department of Radiation Oncology, Peking University Third Hospital, Beijing, China.
  1. Address correspondence and reprint requests to Lihong Zhu, MD, Department of Radiation Oncology, Peking University Third Hospital, No 49 Huayuanbei Rd, Haidian District, 100191, Beijing, China. E-mail: zhulihong510@163.com.

Abstract

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.

  • HeLa
  • Cepharanthine
  • Radiosensitization
  • STAT3
  • COX-2

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Footnotes

  • The authors declare no conflicts of interest.

  • Supplemental digital content is available for this article. Direct URL citation appears in the printed text and is provided in the HTML and PDF versions of this article on the journal’s Web site (www.ijgc.net).

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