山奈酚通过激活 PPARγ/PTEN/AKT 通路对膀胱癌碳酸酐酶 IX 表达和肿瘤发生的影响。

Effect of isorhamnetin on carbonic anhydrase IX expression and tumorigenesis of bladder cancer by activating PPARγ/PTEN/AKT pathway.

机构信息

Department of Urology, the Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong, China.

Department of Urology, Shidao People's Hospital of Rongcheng, Weihai, Shandong, China.

出版信息

Tissue Cell. 2023 Jun;82:102048. doi: 10.1016/j.tice.2023.102048. Epub 2023 Mar 2.

DOI:10.1016/j.tice.2023.102048

PMID:36905861

Abstract

BACKGROUND

To clarify the research prospect and mechanism analysis of isorhamnetin as a therapeutic drug for bladder cancer.

METHODS

Firstly, the effects of different concentrations of isorhamnetin on the expression of PPARγ/PTEN/Akt pathway protein, CA9, PPARγ, PTEN and AKT protein were discussed by western blot. The effects of isorhamnetin on the growth of bladder cells were also analyzed. Secondly, we verified whether the effect of isorhamnetin on CA9 was related to PPARγ/PTEN/Akt pathway by western blot, and the mechanism of isorhamnetin on the growth of bladder cells is related to this pathway by CCK8, cell cycle and ball formation experiment. Further, nude mouse model of subcutaneous tumor transplantation was constructed to analyze the effects of isorhamnetin, PPAR and PTEN on 5637 cell tumorigenesis and the effects of isorhamnetin on tumorigenesis and CA9 expression through PPARγ/PTEN/Akt pathway.

RESULTS

Isorhamnetin inhibited the development of bladder cancer, and regulated the expression of PPAR, PTEN, AKT, CA9. Isorhamnetin inhibits cell proliferation and the transition of cells from G0/G1 phase to S phase, and tumor sphere formation. Carbonic anhydrase IX is a potential downstream molecule of PPARγ/PTEN/AKT pathway. Overexpression of PPARγ and PTEN inhibited expression of CA9 in bladder cancer cells and tumor tissues. Isorhamnetin reduced CA9 expression in bladder cancer via PPARγ/PTEN/AKT pathway, thereby inhibiting bladder cancer tumorigenicity.

CONCLUSION

Isorhamnetin has the potential to become a therapeutic drug for bladder cancer, whose antitumor mechanism is related to PPARγ/PTEN/AKT pathway. Isorhamnetin reduced CA9 expression in bladder cancer via PPARγ/PTEN/AKT pathway, thereby inhibiting bladder cancer tumorigenicity.

摘要

背景

阐明山奈酚作为膀胱癌治疗药物的研究前景和机制分析。

方法

首先，通过 Western blot 探讨不同浓度山奈酚对 PPARγ/PTEN/Akt 通路蛋白、CA9、PPARγ、PTEN 和 AKT 蛋白表达的影响，分析山奈酚对膀胱细胞生长的影响。其次，通过 Western blot 验证山奈酚对 CA9 的作用是否与 PPARγ/PTEN/Akt 通路有关，通过 CCK8、细胞周期和球形成实验验证山奈酚对膀胱细胞生长的作用与该通路有关。进一步构建裸鼠皮下肿瘤移植模型，分析山奈酚、PPAR 和 PTEN 对 5637 细胞肿瘤发生的影响及山奈酚通过 PPARγ/PTEN/Akt 通路对肿瘤发生和 CA9 表达的影响。

结果

山奈酚抑制膀胱癌的发展，调节 PPAR、PTEN、AKT、CA9 的表达。山奈酚抑制细胞增殖和细胞从 G0/G1 期向 S 期的转化，以及肿瘤球形成。碳酸酐酶 9 是 PPARγ/PTEN/AKT 通路的潜在下游分子。过表达 PPARγ 和 PTEN 抑制膀胱癌细胞和肿瘤组织中 CA9 的表达。山奈酚通过 PPARγ/PTEN/AKT 通路降低膀胱癌细胞中 CA9 的表达，从而抑制膀胱癌的致瘤性。