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中国临床药理学与治疗学 ›› 2007, Vol. 12 ›› Issue (8): 877-882.

• 基础研究 • 上一篇    下一篇

5-氟脲嘧啶诱导人结直肠癌Lovo细胞凋亡的分子机制

王索安1, 宋清2, 张晓文2, 赵明2, 刘永年3, 赵海龙3, 张伟3   

  1. 1浙江高等医学专科学校病理教研室, 杭州 310053, 浙江;
    2广州中医药大学基础医学院, 广州 510405, 广东;
    3青海大学医学院病理教研室, 西宁 810000, 青海
  • 收稿日期:2007-03-22 修回日期:2007-06-13 出版日期:2007-08-26 发布日期:2020-10-27
  • 作者简介:王索安,男,教授,硕导,主要从事肿瘤病理及抗肿瘤药物研究。Tel:0571-87692676 E-mail:suoanwang@hotmail.com
  • 基金资助:
    教育部科学技术重点项目(2001133)

Study on apoptosis of human colorectal carcinoma cell line lovo induced by 5-Fluorouracil and its molecular mechanisms

WANG Suo-an1, SONG Qing2, ZHANG Xiao-wen2, ZHAO Ming3, LIU Yong-nian3, ZHAO Hai-long3, ZHANG Wei3   

  1. 1Department of Pathology, Zhejiang College of Medicine, Hangzhou 310013, Zhejiang, China;
    2Department of Basic Medicine, Guangzhou University of Traditional Chinese Medicine, Guangzhou 510405, Guangdong, China;
    3Department of Pathology, Medical College of Qinghai University, Xining 810000, Qinghai, China
  • Received:2007-03-22 Revised:2007-06-13 Online:2007-08-26 Published:2020-10-27

摘要: 目的: 研究5-氟脲嘧啶(5-FU) 对体外培养人结直肠癌Lovo 细胞增殖的抑制作用及诱导凋亡的分子机制。方法: 分别采用MTT 法检测细胞活力,用光镜、电镜观察凋亡细胞的组织形态学和超微结构变化, 流式细胞术(FCM) 分析诱导细胞凋亡的细胞周期阻滞点, 免疫组化SP 法检测对Lovo 细胞增殖核抗原(PCNA) 及凋亡相关基因蛋白P53、Bax 表达的影响。结果: 5-FU 能抑制Lovo 细胞生长, 光镜与电镜结果均显示凋亡细胞明显增多, FCM 分析Lovo 细胞经5-FU 诱导后凋亡百分率显著增加, 并具有剂量和时间的效应。免疫组化显示5-FU 组细胞PCNA 表达明显低于对照组、Bax 表达明显升高(P<0.01), 而P53 在诱导前后均无表达。结论: 5-FU 能抑制Lovo 细胞增殖并通过诱导该细胞系凋亡发挥抗肿瘤效应, 激活bax 基因和G2/M 期阻滞是其诱导Lovo 细胞凋亡的重要机制。

关键词: 5-氟脲嘧啶, 结直肠癌, 凋亡, P53, Bax

Abstract: AIM: To study the molecular mechanism of the cell proliferation inhibition and apoptosis induction effects of 5-Fluorouracil (5-Fu) on human colorectal carcinoma cell line Lovo in vitro. METHODS: By means of MTT reduction assay, the effect of 5-Fu on the proliferation of Lovo cells was measured.Morphological changes were observed under the electron and opitical microscopy. Apoptotic cell cycle arrest was detected by Flow Cytometry.The expressions of PCNA, P53 and Bax were determined by immunohistochemical S-P method. RESULTS: 5-Fu could significantly inhibit the proliferation and aggressivity of Lovo cells and the inhibitory effects were dose-and-time-dependent.The action was mainly attribute to cell apoptosis as proved by flow cytometry assay and electron microscopy.The PCNA expressions of cells of experimental groups were lower than those of control group.The expression of apoptosis related gene bax of the experimental groups was significantly enhanced (P<0.01).The expression of P53 was not found in both experimental and control groups. CONCLUSION: 5-fu could significantly inhibit the proliferation and aggressivity of Lovo cells.Activation of apoptosis related gene bax and G2/M phase arrest were important mechanisms of 5-fu-induced apoptosis.

Key words: 5-Fluorouracil, apoptosis, colorectal colorectal, P53, Bax

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