|本期目录/Table of Contents|

[1]陆益,于佳熙,梁政.氯丙嗪对膀胱癌BT-B细胞迁移功能的影响[J].天津医科大学学报,2022,28(06):621-626.
　LU Yi,YU Jia-xi,LIANG Zheng.The effect of chlorpromazine on the migration of BT-B cellsin bladder cancer[J].Journal of Tianjin Medical University,2022,28(06):621-626.
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氯丙嗪对膀胱癌BT-B细胞迁移功能的影响(PDF)
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《天津医科大学学报》[ISSN:1006-8147/CN:12-1259/R]

卷:
28卷
期数:
2022年06期
页码:
621-626
栏目:
基础医学
出版日期:
2022-11-20

文章信息/Info

Title:
The effect of chlorpromazine on the migration of BT-B cellsin bladder cancer
文章编号:
1006-8147(2022)06-0621-06
作者:
陆益1; 于佳熙2; 梁政2
1.天津医科大学研究生院，天津 300070；2.天津医科大学总医院耳鼻咽喉科，天津300052
Author(s):
LU Yi1; YU Jia-xi2; LIANG Zheng2
（1.Graduate School，Tianjin Medical University，Tianjin 300070，China；2.Department of Otorhinolaryngology，General Hospital，Tianjin Medical University，Tianjin 300052，China）
关键词:
氯丙 嗪; YAP1; RAP1A; EMT; 膀胱癌
Keywords:
chlorpromazine; YAP1 ; RAP1A ; EMT; bladder cancer
分类号:
R73-36
DOI:
-
文献标志码:
A
摘要:
目的：探讨盐酸氯丙嗪对膀胱癌BT-B细胞迁移功能的影响及其机制。方法：用不同浓度的氯丙嗪处理膀胱癌BT-B细胞，通过MTT、细胞划痕和Transwell迁移实验验证氯丙嗪对细胞生长和迁移功能的影响。蛋白印迹实验和RT-qPCR实验验证氯丙嗪对Yes相关蛋白1（YAP1)和Ras相关蛋白1A（RAP1A）蛋白表达水平和mRNA表达水平的影响。免疫荧光实验验证氯丙嗪对YAP1细胞亚定位的影响。质粒转染实验验证YAP1和RAP1A与上皮间质转化（EMT）的调控关系。结果：氯丙嗪可抑制膀胱癌BT-B细胞的生长（t=11.53，P<0.001；t=35.83，P<0.000 1；t=36.1，P<0.000 1；t=194.6，P<0.000 1）和迁移（t=5.80，P<0.01；t=7.43，P<0.01；t=5.13，P<0.01；t=6.61，P<0.01；t=18.51，P<0.000 1；t=19.04，P<0.000 1）；与对照组相比，氯丙嗪作用于BT-B细胞后，YAP1（t=6.12，P<0.05；t=7.64，P<0.05）和RAP1A（t=4.87，P<0.05；t=8.30，P<0.05）的蛋白表达水平和mRNA表达水平（t=21.13，P<0.001；t=40.59，P<0.001）均显著降低；与对照组相比，氯丙嗪给药处理2 h后YAP1的荧光表达明显变弱；与对照组相比，YAP1表达增加后RAP1A蛋白（t=9.05，P<0.05）和EMT相关分子N-cadherin蛋白、Slug+snail蛋白（t=7.24，P<0.05；t=5.57，P<0.05）表达均显著增加，而YAP1敲低后RAP1A蛋白（t=4.36，P<0.05）、N-cadherin蛋白和Slug+snail蛋白（t=4.50，P<0.05；t=4.49，P<0.05）表达均显著降低。结论：氯丙嗪可通过 YAP1调节RAP1A抑制膀胱癌的迁移，可能是治疗膀胱癌的一种新选择。
Abstract:
Objective： To investigate the effect and mechanism of chlorpromazine（CPZ） on the migration of bladder cancer BT-B cells. Methods：The MTT，wound healing and Transwell migration assays were used to determine the growth and migration of BT-B cells with different concentrations of CPZ treatment. Western blotting and RT-qPCR assays were used to determine the protein and mRNA expressions of Yes-associated protein 1（YAP1） and Ras-associated protein 1A（RAP1A）. Immunofluorescence assay was used to verify the effect of CPZ on the sublocalization of YAP1. Plasmid transfection experiment was used to verify the regulatory relationship between YAP1 and RAP1A and epithelial-mesenchymal transition（EMT）. Results：CPZ inhibited the growth（t=11.53，P<0.001；t=35.83，P<0.000 1；t=36.1，P<0.000 1；t=194.6，P<0.000 1） and migration of bladder cancer BT-B cells（t=5.80，P<0.01；t=7.43，P<0.01；t=5.13，P<0.01；t=6.61，P<0.01；t=18.51，P<0.000 1；t=19.04，P<0.000 1）. Compared with the control group，the expression of YAP1（t=6.12，P<0.05；t=7.64，P<0.05） and RAP1A（t=4.87，P<0.05；t=8.30，P<0.05），and the mRNA expression levels（t=21.13，P<0.001；t=40.59，P<0.001） of them were significantly decreased after treated with CPZ. Compared with the control group，the fluorescent expression of YAP1 was weaker with CPZ treatment at 2 hours. Compared with the control group，overexpression of YAP1 significantly increased the protein expressions of RAP1A（t=9.05，P<0.05），EMT-related molecules N-cadherin and Slug+snail（t=7.24，P<0.05；t=5.57，P<0.05），while the expression of RAP1A protein （t=4.36，P<0.05），N-cadherin protein and Slug+snail protein（t=4.50，P<0.05；t=4.49，P<0.05） were significantly decreased after the knockdown of YAP1. Conclusion：CPZ can inhibit the migration of bladder cancer by regulating RAP1A through YAP1. CPZ may be a new option for treating bladder cancer.

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备注/Memo

备注/Memo:
基金项目 天津市自然科学基金（17JCYBJC25600）
作者简介 陆益（1994-），女，硕士在读，研究方向：肿瘤发病机制；
通信作者：梁政，E-mail：liangzheng01@tmu.edu.cn。
更新日期/Last Update: 2022-11-20