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山东大学学报（医学版） ›› 2016, Vol. 54 ›› Issue (5): 1-5.doi: 10.6040/j.issn.1671-7554.0.2016.222

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重组腺病毒35型纤毛突蛋白增强西妥昔单抗的抗卵巢癌作用

肖俊超1,蒋雯2,南慧3,王培荣1   

  1. 1.山东大学第二医院小儿内科, 山东 济南 250033;2.山东大学第二医院中心实验室, 山东 济南 250033;3.聊城市人民医院小儿内科, 山东 聊城 252002
  • 收稿日期:2016-03-04 出版日期:2016-05-16 发布日期:2016-05-16
  • 通讯作者: 王培荣. E-mail:peirong8@163.com E-mail:peirong8@163.com
  • 基金资助:
    国家自然科学基金(81272577)

A recombinant adenovirus fiber knob protein sensitizes ovarian cancer cells to cetuximab therapy

XIAO Junchao1, JIANG Wen2, NAN Hui3, WANG Peirong1   

  1. 1. Department of Pediatrics;
    2. Central Lab, Second Hospital of Shandong University, Jinan 250033, Shandong, China;
    3. Department of Pediatrics, Liaocheng Peoples Hospital, Liaocheng 252002, Shandong, China
  • Received:2016-03-04 Online:2016-05-16 Published:2016-05-16

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摘要： 目的 探讨重组腺病毒35型纤毛突蛋白(Ad35K++)能否增强西妥昔单抗诱导补体依赖的细胞毒效应(CDC)对卵巢癌细胞的抗肿瘤作用。 方法 将Ad35K++与SK-OV-3卵巢癌细胞进行孵育,采用流式细胞术测定CD46分子表达水平变化,确定最佳干预时间点。联合Ad35K++与西妥昔单抗和正常人血清处理卵巢癌细胞,采用MTT法检测细胞增殖抑制率,流式细胞术检测细胞凋亡比例,Western blotting法检测凋亡通路蛋白表达水平。 结果 Ad35K++可抑制卵巢癌细胞表面CD46分子表达水平。联合应用可以增强西妥昔单抗介导的补体杀伤效应,明显抑制SK-OV-3细胞的增殖效应,CDC效应介导的细胞凋亡比例上调,凋亡相关蛋白Bax、cleaved-caspase3以及cleaved-PARP表达水平明显上调,Bcl-2表达水平明显下调。 结论 Ad35K++可通过抑制细胞表面的CD46分子表达增强西妥昔单抗对卵巢癌的细胞毒作用。

关键词: 西妥昔单抗, 卵巢肿瘤, 重组腺病毒35型纤毛突蛋白, CD46分子

Abstract: Objective To investigate whether Ad35K++ could enhance complement dependent cytotoxicity(CDC)triggered by cetuximab to ovarian cancer, and to explore the possible mechanisms. Methods The SK-OV-3 cells were incubated with Ad35K++, followed by cetuximab and normal human serum(NHS)treatment. CD46 expression of SK-OV-3 cells and apoptosis rate were measured with flow cytometry. The cell inhibition rate was detected with MTT array. The expression of Bcl-2 family and activation of caspase-3 were tested with Western blotting. Results CD46 level on the surface of SK-OV-3 cells was dramatically decreased after being incubated with Ad35K++. Ad35K++ sensitized SK-OV-3 cells to CDC triggered by cetuximab in vitro and enhanced complement mediated apoptosis. The expressions of Bax, cleaved-caspase 3, cleaved-PARP were upregulated and the expression of Bcl-2 was down-regulated. Conclusion Ad35K++ could enhance CDC triggered by cetuximab to ovarian cancer via the activation of mitochondria-mediated apoptotic pathway.

Key words: Ovarian cancer, CD46, Cetuximab, Ad35K++

中图分类号: 

  • R737.3
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