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线粒体靶向小分子IR-780对顺铂耐药膀胱癌细胞的杀伤效应
Anti-tumor effect of mitochondrial targeted small molecule IR-780 on cisplatin-resistant bladder cancer cells
- 第三军医大学学报 2021年43卷第23期 页码：2570-2576
- 作者机构：
401120 重庆，重庆医科大学附属第三医院泌尿外科
- 作者简介：
[支轶，E-mail: urolzhi@aliyun.com ZHI Yi, E-mail: urolzhi@aliyun.com
- 基金信息：重庆医科大学附属第三医院科研孵化项目(KY08026);2021年渝北区科技计划项目(2021(农社)38)
DOI：10.16016/j.1000-5404.202106190
中图分类号： R737.14;R965;R979.19收稿：2021-06-24，
修回：2021-09-01，
纸质出版：2021-12-15
- 稿件说明：
移动端阅览
黄垣堤, 沈崇星, 李金瑾, 等. 线粒体靶向小分子IR-780对顺铂耐药膀胱癌细胞的杀伤效应[J]. 第三军医大学学报, 2021,43(23):2570-2576.
Yuandi HUANG, Chongxing SHEN, Jinjin LI, et al. Anti-tumor effect of mitochondrial targeted small molecule IR-780 on cisplatin-resistant bladder cancer cells[J]. Journal of Third Military Medical University, 2021, 43(23): 2570-2576.
黄垣堤, 沈崇星, 李金瑾, 等. 线粒体靶向小分子IR-780对顺铂耐药膀胱癌细胞的杀伤效应[J]. 第三军医大学学报, 2021,43(23):2570-2576. DOI： 10.16016/j.1000-5404.202106190.
Yuandi HUANG, Chongxing SHEN, Jinjin LI, et al. Anti-tumor effect of mitochondrial targeted small molecule IR-780 on cisplatin-resistant bladder cancer cells[J]. Journal of Third Military Medical University, 2021, 43(23): 2570-2576. DOI： 10.16016/j.1000-5404.202106190.
摘要
目的
2
探讨线粒体靶向小分子IR-780对顺铂耐药T24膀胱癌细胞株(T24/DPP)的杀伤效应及其作用机制。
方法
2
通过顺铂反复间断刺激T24细胞，构建T24/DPP耐药细胞株，以不同浓度的IR-780处理细胞，CCK-8法检测细胞活力，划痕实验检测细胞迁移能力，荧光共聚焦确定IR-780的亚细胞器定位，流式细胞术测定细胞凋亡以及线粒体活性氧水平。对6~8周龄雄性裸鼠皮下注射T24/DPP细胞建立动物荷瘤模型，将荷瘤小鼠完全随机化分组：对照组、阿霉素组和IR-780组分别腹腔注射5 mg/kg PBS、阿霉素和IR-780，隔天1次。通过近红外活体成像以及荧光共聚焦检测IR-780的蓄积特性，并对肿瘤生长情况进行监测。
结果
2
① 细胞实验结果显示，IR-780抑制T24/DPP细胞增殖与迁移，且抑制作用呈明显的剂量效应关系(
P
<
0.05)。IR-780选择性积聚在T24/DPP细胞的线粒体中。随着IR-780浓度的增加，T24/DDP细胞线粒体活性氧的产生和细胞凋亡率均随之增加(
P
<
0.05)。②体内实验结果显示，近红外活体成像和肿瘤组织冰冻切片显示IR-780可优先聚集于裸鼠T24/DDP皮下移植瘤，并且IR-780组小鼠肿瘤的体积及质量均明显小于对照组(
P
<
0.05)和阿霉素组(
P
<
0.05)。
结论
2
IR-780能显著抑制T24/DPP细胞和裸鼠皮下肿瘤的生长，且线粒体通路可能参与了IR-780诱导T24/DPP细胞发生凋亡的过程。
Abstract
Objective
2
To study the anti-tumor effect of IR-780
a mitochondrial targeting small molecule
on cisplatin-resistant T24 cell line (T24/DPP).
Methods
2
T24/DPP cell line was constructed by repeated and discontinuous stimulation of T24 cells with cisplatin. After the drug-resistant cells were treated with different concentrations of IR-780
cell viability was detected by CCK-8 assay and cell migration was measured by wound healing assay. The suborganelle localization of IR-780 was determined by confocal fluorescence microscopy with aid of mitotracker treatment. Cell apoptosis and production of mitochondrial reactive oxygen species (ROS) were determined by flow cytometry. T24/DPP cells were injected subcutaneously into 6-~8-week-old male nude mice to establish a tumor-bearing nude mouse model. The tumor-bearing mice were randomly divided into 3 groups
including control group (5 mg/kg PBS)
DOX group (5 mg/kg DOX) and IR-780 group (5 mg/kg IR-780). After intraperitoneal administration of IR-780
the accumulation of IR-780 were detected by near-infrared
in vivo
imaging system and confocal fluorescence microscopy
while the tumor volume and weight were measured.
Results
2
①
In vitro
IR-780 inhibited the proliferation and migration of T24/DPP cells in a dose-dependent manner (
P
<
0.05). IR-780 was selectively accumulated in the mitochondria of T24/DPP cells. With the increase of IR-780 concentration
the production of mitochondrial ROS and the rate of apoptosis in T24/DDP cells were increased (
P
<
0.05). ②
In vivo
near-infrared imaging and frozen sections of tumor tissue showed that IR-780 preferentially accumulated in the tumor of tumor-bearing nude mouse model. The tumor volume and weight of the IR-780 group were significantly less and lower when compared with the control group (
P
<
0.05) and DOX group (
P
<
0.05).
Conclusion
2
IR-780 can significantly inhibit the growth of T24/DDP cells and subcutaneous tumor xenografts in nude mice
and the mitochondrial pathway might be involved in the apoptosis of T24/DPP cells induced by IR-780.
关键词
Keywords
references
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