生物学杂志 ›› 2020, Vol. 37 ›› Issue (3): 58-.doi: 10.3969/j.issn.2095-1736.2020.03.058

• 研究报告 • 上一篇    下一篇

三氧化二砷抑制秀丽线虫生殖细胞肿瘤样增殖

  

  1. 1. 安徽大学 学报(自然科学版)编辑部, 合肥 230039; 2. 淮南师范学院 生物工程学院,淮南 232038; 3. 淮南师范学院 资源与环境生物技术安徽普通高校重点实验室, 淮南232038
  • 出版日期:2020-06-18 发布日期:2020-06-10
  • 通讯作者: 王顺昌,博士,教授,研究方向为模式动物与环境相互作用机制,E-mail: scwangl@hotmail.com
  • 作者简介:于敏,副教授,研究方向为生理与毒理学及编辑学,E-mail: yuminwyp@163.com
  • 基金资助:
    国家自然科学基金资助项目(21077040);安徽省教育厅自然科学重点研究项目(KJ2017A464)

Inhibition effects of arsenic trioxide on gonad tumorous proliferation of the nematode Caenorhabditis elegans

  1. 1. The Editorial Office of Journal (Natural Science Edition), Anhui University, Hefei 230039;2. School of Biological Engineering, Huainan Normal University, Huainan 232038;3. Key Laboratory of Bioresource and Environmental Biotechnology of Anhui Higher
    Education Institutes, Huainan Normal University, Huainan 232038, China
  • Online:2020-06-18 Published:2020-06-10

摘要: 无机砷是环境致癌剂,砷暴露可导致包括癌症在内的多种疾病高发。但一些砷化合物如三氧化二砷(ATO)却可以有效治疗急性早幼性白血病等多种癌症。肿瘤抑制基因p53在介导癌症治疗中具有重要作用,但p53基因在ATO治疗中的作用机制尚不完全明了。模式生物秀丽线虫只具有单个p53基因,是研究机体p53对DNA损伤和细胞周期调控作用的良好模型。以gld-1(q485)线虫突变体为对象,研究ATO对其生殖腺肿瘤样增殖的影响,结果表明,ATO处理延长了gld-1(q485)突变体的寿命,抑制了生殖腺的肿瘤样增殖。进一步的研究表明,ATO处理抑制线虫生殖细胞增殖,并具有显著的剂量效应和时间效应;ATO处理还诱导了线虫生殖细胞凋亡。利用线虫CEP-1/p53基因突变品系,结合RNAi基因敲除技术,发现ATO诱导了不依赖于CEP-1/p53的生殖细胞周期停滞和依赖于CEP-1/p53的细胞凋亡。

关键词: 三氧化二砷(ATO), 秀丽线虫, CEP-1/p53, 细胞周期停滞, 细胞凋亡

Abstract: Inorganic arsenic has been shown as an environmental carcinogen, exposure to arsenic can resulted in high incidence of multiple diseases including cancer. Paradoxically, several arsenic compounds such as arsenic trioxide have been used effectively to treat promyelocytic leukaemia and other solid tumors. It has been shown that the tumor suppressor p53 plays important roles in cancer therapy. However, the roles of p53 on the treatment effects of ATO are still uncertain. The nematode Caenorhabditis elegans has been shown as a good model for studying the regulative effects of p53 on DNA damage and cell cycle because it has only a single p53-like gene cep-1. In the present study, the therapeutic effects of ATO on the gonad tumorous growth were studied using gld-1(q485) mutated worms. The results presented here indicated that ATO treatment extended the lifespan of gld-1(q485) mutants and inhibited tumorous growth of the gonad. ATO treatment induced cell cycle arrest in a dose- and time-dependent manner. It was also found that ATO treatment resulted in germline apoptosis in worms of N2 and gld-1(q485) mutants. By using worm strains carrying mutated cep-1 alleles plus RNAi double gene knockout, it was found that ATO exerted its antitumor activity on gld-1(q485) mutants through the induction of cell cycle arrest in a CEP-1/p53-independent manner and germline apoptosis in a CEP-1/p53-dependent manner.

Key words: arsenic trioxide, Caenorhabditis elegans, CEP-1/p53, cell cycle arrest, apoptosis

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