| 沉默circPVT1对5-氟尿嘧啶耐药胃癌细胞化疗增敏作用及机制研究 |
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| 引用本文： | 左兴盛,宋志玉,贾海盼,付中华,王振基,马培志.沉默circPVT1对5-氟尿嘧啶耐药胃癌细胞化疗增敏作用及机制研究[J].天津医科大学学报,2021,0(6):574-579,585. |
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| 作者姓名： | 左兴盛 宋志玉 贾海盼 付中华 王振基 马培志 |
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| 作者单位： | （1.河南省人民医院药学部，郑州大学人民医院药学部，郑州450003；2.郑州大学药学院，郑州450000） |
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| 摘 要： | 目的:研究circPVT1对胃癌细胞5-氟尿嘧啶（FU）敏感性的作用及分子机制。方法:采用RT-PCR检测胃癌组织、胃癌细胞BGC823和5-FU抵抗胃癌细胞 BGC823/5-FU 中circPVT1的相对表达水平。沉默circPVT1，采用CCK-8试剂盒检测细胞活性，观察其对细胞活性的影响。采用克隆形成实验检测细胞克隆形成能力。采用TUNEL试剂盒和流式细胞仪检测细胞凋亡情况。采用RT-PCR和Western 印迹检测Bcl-2、Bax 和caspase-3基因mRNA和蛋白的表达水平。沉默circPVT1观察裸鼠皮下移植瘤生长。结果:在5-FU抵抗患者胃癌组织中circPVT1的表达水平明显高于5-FU敏感患者（P＜0.01）。与BGC823细胞相比，circPVT1在BGC823/5-FU细胞中的表达水平明显升高（P＜0.001）。下调circPVT1表达可增强5-FU的细胞毒性（P＜0.05）。与5-FU+si-NC组相比，5-FU+si-circPVT1组BGC823/5-FU细胞的克隆形成能力明显降低（P＜0.05）。5-FU+si-circPVT1组BGC823/5-FU细胞的凋亡数目明显高于5-FU+si-NC组（P＜0.01）。沉默circPVT1，与5-FU+si-NC组相比，5-FU+si-circPVT1组BGC823/5-FU细胞中Bcl-2的mRNA和蛋白表达水平明显降低，Bax和caspase-3的mRNA和蛋白表达水平明显升高（P<0.01）。裸鼠移植瘤实验结果显示，5-FU+si-circPVT1组移植瘤体积和重量明显低于5-FU+si-NC组（P＜0.05）。结论:沉默circPVT1可以通过调控Bcl-2、Bax和caspase-3的表达，增强BGC823/5-FU细胞对5-FU的敏感性。
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| 关 键 词： | circPVT1 胃癌 5-氟尿嘧啶 耐药 |
The sensitizing effect and mechanism of silencing of circPVT1 on 5-fluorouracil chemosensitivity in gastric cancer cells |
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| ZUO Xing-sheng,SONG Zhi-yu,JIA Hai-pan,FU Zhong-hua,WANG Zhen-ji,MA Pei-zhi.The sensitizing effect and mechanism of silencing of circPVT1 on 5-fluorouracil chemosensitivity in gastric cancer cells[J].Journal of Tianjin Medical University,2021,0(6):574-579,585. |
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| Authors: | ZUO Xing-sheng SONG Zhi-yu JIA Hai-pan FU Zhong-hua WANG Zhen-ji MA Pei-zhi |
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| Affiliation: | （1.Department of Pharmacy，Henan People′s Hospital，People′s Hospital of Zhengzhou University，Zhengzhou 450003，China；2.School of Medicine，Zhengzhou University，Zhengzhou 450000，China） |
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| Abstract: | Objective: To analyze the effects and molecular mechanism of circPVT1 on 5-fluorouracil（FU） sensitivity of gastric cancer cells. Methods: RT-PCR was used to detect the relative expression level of circPVT1 in gastric cancer tissues，gastric cancer cells（BGC823） and 5-FU resistant gastric cancer cells（BGC823/5-FU）. The CCK-8 kit was used to detect cell viability. The clone formation experiment was used to detect the ability of cell proliferation. TUNEL kit and flow cytometer were used to detect cell apoptosis. RT-PCR and Western blotting were used to detect the mRNA and protein expression of Bcl-2，Bax and caspase-3 genes. Subcutaneous tumor growth in nude mice was used to assess the effect of circPVT1. Results: Compared with gastric cancer patients showing sensitivity to 5-FU，the expression of circPVT1 was much higher in gastric cancer tissues of patients showing resistance to 5-FU（P＜0.01）. The expression of circPVT1 was higher in BGC823/5-FU cells as compared with that in BGC823 cells（P＜0.001）.Downregulation of circPVT1 expression enhanced the cytotoxicity of 5-FU（P<0.05）. Compared with 5-FU+si-NC group，the cell clone formation ability of BGC823/5-FU cells in 5-FU+si-circPVT1 group was significantly decreased（P<0.05）. The apoptosis number of BGC823/5-FU cells in 5-FU+si-circPVT1 group was significantly higher than that in 5-FU+si-NC group（P<0.01）. After silencing of circPVT1，compared with the 5-FU+si-NC group，and the Bcl-2 mRNA and protein expression in the 5-FU+si-circPVT1 group were significantly reduced in BGC823/5-FU cells，the mRNA and protein expression of Bax and caspase-3 were significantly increased（P<0.01）. The experimental results of tumor transplantation in nude mice showed that the volume and weight of transplanted tumor in 5-FU+si-circPVT1 group were significantly lower than those in 5-FU+si-NC group（P<0.05）. Conclusion: Silencing of circPVT1 can enhance the sensitivity of BGC823/5-FU cells to 5-FU trough regulating Bcl-2，Bax and caspase-3. |
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| Keywords: | circular PVT1 gastric cancer 5-fluorouracil drug resistance |
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