Artemisinin derivative artesunate induces radiosensitivity in cervical cancer cells in vitro and in vivo

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• 作者：Judong Luo (4) (4)
  Wei Zhu (4)
  Yiting Tang (4)
  Han Cao (4)
  Yuanyuan Zhou (4)
  Rong Ji (4)
  Xifa Zhou (4)
  Zhongkai Lu (4)
  Hongying Yang (4)
  Shuyu Zhang (4)
  Jianping Cao (4) (4)
  
• 关键词：Artesunate (ART) ; Cervical cancer ; Radiosensitivity ; Cell cycle ; Apoptosis
• 刊名：Radiation Oncology
• 出版年：2014
• 出版时间：December 2014
• 年：2014
• 卷：9
• 期：1
• 全文大小：1,491 KB
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• 作者单位：Judong Luo (4) (4)
  Wei Zhu (4)
  Yiting Tang (4)
  Han Cao (4)
  Yuanyuan Zhou (4)
  Rong Ji (4)
  Xifa Zhou (4)
  Zhongkai Lu (4)
  Hongying Yang (4)
  Shuyu Zhang (4)
  Jianping Cao (4) (4)
  
  4. School of Radiation Medicine and Protection, Medical College of Soochow University, 199 Ren’ai Rd, Suzhou, 215123, China
  
• ISSN：1748-717X

文摘

Objective Cervical cancer is the third most common type of cancer in women worldwide and radiotherapy remains its predominant therapeutic treatment. Artesunate (ART), a derivative of artemisinin, has shown radiosensitization effect in previous studies. However, such effects of ART have not yet been revealed for cervical cancer cells. Methods The effect of ART on radiosensitivity of human cervical cancer cell lines HeLa and SiHa was assessed using the clonogenic assay. Cell cycle progression and apoptosis alterations were analyzed by flow cytometry. For in vivo study, HeLa or SiHa cells were inoculated into nude mice to establish tumors. Tissues from xenografts were obtained to detect the changes of microvessel density, apoptosis and cell cycle distribution. Microarray was used to analyze differentially expressed genes. Results ART increased the radiosensitivity of HeLa cells (SER =-.43, P <-.001) but not of SiHa cells. Apoptosis and the G2-M phase transition induced by X-ray irradiation (IR) were enhanced by ART via increased Cyclin B1 expression in HeLa cells. Tumor growth of xenografts from HeLa but not SiHa cells was significantly inhibited by irradiation combined with ART (tumor volume reduction of 72.34% in IR-?ART group vs. 41.22% in IR group in HeLa cells and 48.79% in IR-?ART group vs. 44.03% in IR alone group in SiHa cells). Compared with the irradiated group, cell apoptosis was increased and the G2/M cell cycle arrest was enhanced in the group receiving irradiation combined with ART. Furthermore, compared with radiation alone, X-ray irradiation plus ART affected the expression of 203 genes that function in multiple pathways including RNA transport, the spliceosome, RNA degradation and p53 signaling. Conclusion ART potently abrogates the G2 checkpoint control in HeLa cells. ART can induce radiosensitivity of HeLa cells in vitro and in vivo.