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韩峥, 黄晓东, 刘蒙, 朱庆曦, 谭洁, 刘维洁, 陈巍, 邹艳丽, 蔡一珊, 黄莎莎, 田霞. 那可丁对人结肠癌5-Fu耐药细胞株HT-29/5-Fu、LoVo/5-Fu及SW480/5-Fu耐药性的影响[J]. 肿瘤防治研究, 2019, 46(8): 696-701. DOI: 10.3971/j.issn.1000-8578.2019.18.1927
引用本文: 韩峥, 黄晓东, 刘蒙, 朱庆曦, 谭洁, 刘维洁, 陈巍, 邹艳丽, 蔡一珊, 黄莎莎, 田霞. 那可丁对人结肠癌5-Fu耐药细胞株HT-29/5-Fu、LoVo/5-Fu及SW480/5-Fu耐药性的影响[J]. 肿瘤防治研究, 2019, 46(8): 696-701. DOI: 10.3971/j.issn.1000-8578.2019.18.1927
HAN Zheng, HUANG Xiaodong, LIU Meng, ZHU Qingxi, TAN Jie, LIU Weijie, CHEN Wei, ZOU Yanli, CAI Yishan, HUANG Shasha, TIAN Xia. Effect of Noscapine on Drug Resistance of 5-Fluorouracil-resistant Human Colon Cancer Cell Lines HT-29/5-Fu, LoVo/5-Fu and SW480/5-Fu[J]. Cancer Research on Prevention and Treatment, 2019, 46(8): 696-701. DOI: 10.3971/j.issn.1000-8578.2019.18.1927
Citation: HAN Zheng, HUANG Xiaodong, LIU Meng, ZHU Qingxi, TAN Jie, LIU Weijie, CHEN Wei, ZOU Yanli, CAI Yishan, HUANG Shasha, TIAN Xia. Effect of Noscapine on Drug Resistance of 5-Fluorouracil-resistant Human Colon Cancer Cell Lines HT-29/5-Fu, LoVo/5-Fu and SW480/5-Fu[J]. Cancer Research on Prevention and Treatment, 2019, 46(8): 696-701. DOI: 10.3971/j.issn.1000-8578.2019.18.1927

那可丁对人结肠癌5-Fu耐药细胞株HT-29/5-Fu、LoVo/5-Fu及SW480/5-Fu耐药性的影响

Effect of Noscapine on Drug Resistance of 5-Fluorouracil-resistant Human Colon Cancer Cell Lines HT-29/5-Fu, LoVo/5-Fu and SW480/5-Fu

  • 摘要:
    目的 探讨那可丁(Nos)对人结肠癌5-氟尿嘧啶(5-Fu)耐药株耐药性的影响及其机制。
    方法 构建人结肠癌耐药株HT-29/5-Fu、LoVo/5-Fu及SW480/5-Fu,MTT法筛选出Nos对各组细胞的半数抑制浓度(IC50),观察细胞形态变化,利用流式细胞仪检测细胞周期及凋亡水平;RT-qPCR及Western blot检测细胞P38表达和激活水平,以及耐药相关蛋白的表达。
    结果 成功构建耐药细胞株HT-29/5-Fu、LoVo/5-Fu和SW480/5-Fu。与对照组比较,Nos干预后的结肠癌耐药细胞株HT-29/5-Fu、LoVo/5-Fu及SW480/5-Fu细胞周期明显阻滞在G0/G1期(P < 0.01),凋亡率升高,而P38表达及磷酸化受到显著抑制(P < 0.01),与耐药相关的多药耐药相关蛋白、肺耐药相关蛋白及P-glycoprotein表达显著降低(P < 0.01)。
    结论 Nos对耐5-Fu的人结肠癌细胞具有一定的毒性作用,降低了耐药细胞耐药性,作用机制可能与抑制P38的表达和磷酸化有关。

     

    Abstract:
    Objective To investigate the effect of Noscapine(Nos) on drug resistance of 5-Fu-resistant human colon cancer cell lines and its mechanism.
    Methods Drug-resistant cell lines HT-29/5-Fu, LoVo/5-Fu and SW480/5-Fu were established. MTT assay was used to test IC50 and cell morphology was observed. Cell cycle and apoptosis were determined by flow cytometry. RT-qPCR and Western blot were used to detect the expression and phosphorylation of P38 and the expression of drug resistance-related proteins.
    Results The drug-resistant cell lines HT-29/5-Fu, LoVo/5-Fu and SW480/5-Fu were successfully constructed. Compared with control group, cell cycle of colon cancer drug-resistant cell lines HT-29/5-Fu, LoVo/5-Fu and SW480/5-Fu after Nos intervention was significantly blocked at G0/G1 phase (P < 0.01), the apoptosis rate was increased, the expression of P38 and phosphorylation were significantly inhibited (P < 0.01), and the expression of MRP, LRP and P-glycoprotein were significantly decreased (P < 0.01).
    Conclusion Noscapine has a certain toxic effect on 5-Fu-resistant human colon cancer cells and reduces drug resistance. The mechanism may be related to the inhibition of P38 expression and phosphorylation.

     

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