中国现代普通外科进展2024,Vol.27Issue(5) :364-368.DOI:10.3969/j.issn.1009-9905.2024.05.006

CP-31398对胆囊癌细胞增殖和转移的影响及机制

Effect and mechanism of CP-31398 on proliferation and metastasis of gallbladder carcinoma cells

孙学娣 曹圣芹 李重阳 刘敬华 何强
中国现代普通外科进展2024,Vol.27Issue(5) :364-368.DOI:10.3969/j.issn.1009-9905.2024.05.006

CP-31398对胆囊癌细胞增殖和转移的影响及机制

Effect and mechanism of CP-31398 on proliferation and metastasis of gallbladder carcinoma cells

孙学娣 1曹圣芹 2李重阳 3刘敬华 4何强4
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作者信息

  • 1. 锦州医科大学(辽宁 锦州 121001);临沂市人民医院 普外科(山东 临沂 276000)
  • 2. 济南市第四人民医院 手足外科(山东 济南 250031)
  • 3. 滨州医学院(山东 烟台 264003);临沂市人民医院 普外科(山东 临沂 276000)
  • 4. 临沂市人民医院 普外科(山东 临沂 276000)
  • 折叠

摘要

目的:研究CP-31398对表达突变型p53GBC-SD和表达野生型p53NOZ胆囊癌细胞株增殖和转移的影响.方法:突变型p53GBC-SD中加入药物CP-31398为CP-31398组,未加药组为对照组;野生型p53NOZ中加入药物CP-31398为CP-31398组,未加药组为对照组.利用CCK8细胞增殖实验检测CP-31398对野生型及突变型p53胆囊癌细胞增殖的影响;利用流式细胞术检测CP-31398对胆囊癌细胞周期及凋亡的影响;利用Transwell实验检测CP-31398对胆囊癌细胞迁移和侵袭的影响;利用Western blot检测CP-31398对p53蛋白表达情况的影响,并对相关机制进行探讨.结果:在突变型p53GBC-SD细胞中,CCK8细胞增殖实验显示CP-31398组较对照组胆囊癌细胞的增殖速度减慢(P<0.01);周期实验显示与对照组相比,CP-31398组的细胞处在S期的细胞比例上升,处在G0、G1期的细胞比例下降,所以细胞在S期被阻断(P<0.001);凋亡实验显示对照组的凋亡率明显低于CP-31398 组(P<0.05);Transwell实验显示,对照组穿过小室的细胞数目高于CP-31398组;Western blot实验说明CP-31398组p53蛋白表达量增加(P<0.05).在表达野生型p53NOZ细胞中,CCK8细胞增殖实验显示CP-31398组较对照组胆囊癌细胞的增殖速度减慢(P<0.001);周期实验显示处在G2、M期的细胞比例明显上升,处于G0、G1期的细胞比例下降,细胞被阻滞于G2、M期(P<0.001);凋亡实验显示对照组的凋亡率是(14.04±3.08)%,CP-31398 组的凋亡率是(34.55±3.30)%(P<0.01);Transwell 实验显示,对照组穿过小室的细胞数目高于CP-31398组;Western blot实验显示CP-31398组p53蛋白表达量增加(P<0.01).结论:CP-31398有效抑制胆囊癌细胞的增殖及转移,并且不依赖p53的突变,且CP-31398对表达野生型p53的NOZ胆囊癌细胞株作用效果较好,可以作为胆囊癌药物治疗的一个新选择.

Abstract

Objective:To investigate the effects of CP-31398 on proliferation and metastasis of gallbladder carcinoma cell lines expressing mutant P53GBC-SD and wild-type p53NOZ.Meth-ods:The effects of CP-31398 on the proliferation of wild-type and mutant p53 gallbladder carci-noma cells were detected by CCK8 cell proliferation assay and clonal formation assay.The effect of CP-31398 on cell cycle and apoptosis of gallbladder carcinoma was detected by flow cytometry.The effects of CP-31398 on the migration and invasion of gallbladder carcinoma cells were detected by scratch,cytoskeleton and Transwell assay.The effect of CP-31398 on the expression of p53 protein was detected by Western blot and the related mechanism was discussed.Results:In mutant P53GBC-SD cells,the proliferation of CCK8 cells showed that the proliferation rate of gallbladder cancer cells in CP-31398 treatment group was slower than that in control group(P<0.01).The cycle experiment showed that compared with the control group,the proportion of cells in S phase in-creased in CP-31398 treatment group,and the proportion of cells in G0 and G1 phase decreased,so the cells were blocked in S phase(P<0.001).Apoptosis experiment showed that the apoptosis rate of control group was lower than CP-31398 treatment group(P<0.05).Transwell experiment showed that the number of cells passing through the cell compartment in the control group was higher than that in the CP-31398 treatment group.Western blot analysis showed that the expression of p53 pro-tein in CP-31398 treatment group was increased(P<0.05).In wild-type p53NOZ cells,the prolifera-tion of CCK8 cells showed that the proliferation rate of gallbladder cancer cells in CP-31398 treat-ment group was slower than that in control group.The number of cell clones in the control group was higher than that in the CP-31398 treatment group(P<0.001).The cycle test showed that the propor-tion of cells in G2 and M phases increased significantly,while the proportion of cells in G0 and G1 phases decreased,and the cells were blocked in G2 and M phases(P<0.001).Apoptosis experiment showed that the apoptosis rate of control group was(14.04±3.08)%,and that of CP-31398 treat-ment group was(34.55±3.30)%(P<0.01).Transwell experiment showed that the number of cells passing through the cell compartment in the control group was higher than that in the CP-31398 treatment group.Western blot analysis showed that the expression of p53 protein in CP-31398 treatment group was increased(P<0.01).Conclusion:CP-31398 can effectively inhibit the prolif-eration and metastasis of gallbladder cancer cells,and is independent of p53 mutation,and CP-31398 has a good effect on NOZ gallbladder cancer cell lines expressing wild-type p53,which can be used as a new drug treatment for gallbladder cancer.

关键词

胆囊肿瘤/p53突变/CP-31398/细胞增殖/肿瘤转移

Key words

Gallbladder tumor/p53 mutation/CP-31398/Cell proliferation/Tumor metastasis

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出版年

2024
中国现代普通外科进展
山东大学

中国现代普通外科进展

CSTPCD
影响因子:0.993
ISSN:1009-9905
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