白术内酯 I 通过靶向热休克蛋白 27 抑制前列腺癌中的上皮-间质转化并增强卡博替尼的抗肿瘤作用。

Atractylenolide I inhibits EMT and enhances the antitumor effect of cabozantinib in prostate cancer targeting Hsp27.

作者信息

Qiao Pengfei, Tian Zhentao

机构信息

The Department of Urology Surgery, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China.

National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, China.

出版信息

Front Oncol. 2023 Jan 6;12:1084884. doi: 10.3389/fonc.2022.1084884. eCollection 2022.

Abstract

OBJECTIVE

To investigate the effect of Hsp27 and the inhibitory effect of Atractylenolide I (ATL-1) on the proliferation of prostate cancer cell DU145 and PC-3.

METHODS

MTT assay was used to detect the inhibitory effect of silencing Hsp27 and ATL-1 on DU145 and PC-3 proliferation of prostate cancer cells. TUNEL detected the apoptosis rate of prostate cancer cell DU145 and PC-3 after silencing Hsp27 and ATL-1 treated. qRT-PCR was used to detect the changes of apoptosis related genes caspase-3, PARP, Bax and Bcl-2 in prostate cancer cell DU145 and PC-3 after the effect of silencing Hsp27 and ATL-1 treated. At the same time, the antitumor effect of ATL-1 combined with cabozantinib was analyzed.

RESULTS

Hsp27 was highly expressed in human prostate cancer. MTT assay showed that ATL-1 inhibited the proliferation of prostate cancer cells DU145 and PC-3 compared with the control group. TUNEL results showed that silencing Hsp27 and ATL-1 treated could significantly promote the apoptosis of prostate cancer cells DU145 and PC-3 compared with the control group. qRT-PCR results showed that compared with the control group, ATL-1 could promote the expression of caspase-3, PARP and Bax in DU145 and PC-3 prostate cancer cells. Inhibition of Hsp27 by ATL-1 reduced cell viability and induced apoptosis. ATL-1 inhibits the antitumor effect of Hsp27 - enhanced cabozantinib. Hsp27 regulates eIF4E and mediates cell protection.

CONCLUSION

Silencing Hsp27 inhibits EMT. ATL-1 can inhibit the malignant evolution of prostate cancer cells by inhibiting Hsp27/eIF4E. ATL-1 also enhanced chemosensitization of cabozantinib in prostate cancer.

摘要

目的

研究热休克蛋白27(Hsp27)的作用以及白术内酯I(ATL-1)对前列腺癌细胞DU145和PC-3增殖的抑制作用。

方法

采用MTT法检测沉默Hsp27和ATL-1对前列腺癌细胞DU145和PC-3增殖的抑制作用。TUNEL法检测沉默Hsp27和ATL-1处理后前列腺癌细胞DU145和PC-3的凋亡率。采用qRT-PCR法检测沉默Hsp27和ATL-1处理后前列腺癌细胞DU145和PC-3中凋亡相关基因半胱天冬酶-3(caspase-3)、聚(ADP-核糖)聚合酶(PARP)、促凋亡蛋白Bax和抗凋亡蛋白Bcl-2的变化。同时,分析ATL-1联合卡博替尼的抗肿瘤作用。

结果

Hsp27在人前列腺癌中高表达。MTT法检测结果显示,与对照组相比,ATL-1抑制了前列腺癌细胞DU145和PC-3的增殖。TUNEL结果显示,与对照组相比,沉默Hsp27和ATL-1处理可显著促进前列腺癌细胞DU145和PC-3的凋亡。qRT-PCR结果显示,与对照组相比,ATL-1可促进DU145和PC-3前列腺癌细胞中caspase-3、PARP和Bax的表达。ATL-1对Hsp27的抑制降低了细胞活力并诱导了凋亡。ATL-1抑制了Hsp27增强的卡博替尼的抗肿瘤作用。Hsp27调节真核翻译起始因子4E(eIF4E)并介导细胞保护。

结论

沉默Hsp27可抑制上皮-间质转化(EMT)。ATL-1可通过抑制Hsp27/eIF4E抑制前列腺癌细胞的恶性进展。ATL-1还增强了卡博替尼在前列腺癌中的化疗敏感性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f9a/9853281/d136618fdb48/fonc-12-1084884-g001.jpg

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