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雷公藤红素通过CAV-1/LOX-1通路减轻肾透明细胞癌的脂质积累和干性。

Celastrol Attenuates Lipid Accumulation and Stemness of Clear Cell Renal Cell Carcinoma via CAV-1/LOX-1 Pathway.

作者信息

Zhang Chan-Juan, Zhu Neng, Wang Yu-Xiang, Liu Le-Ping, Zhao Tan-Jun, Wu Hong-Tao, Liao Duan-Fang, Qin Li

机构信息

Division of Stem Cell Regulation and Application, Department of Pharmacology, School of Pharmacy, Hunan University of Chinese Medicine, Changsha, China.

Department of Urology, The First Hospital of Hunan University of Chinese Medicine, Changsha, China.

出版信息

Front Pharmacol. 2021 Apr 16;12:658092. doi: 10.3389/fphar.2021.658092. eCollection 2021.

DOI:10.3389/fphar.2021.658092
PMID:33935779
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8085775/
Abstract

Clear cell renal cell carcinoma (ccRCC) is characterized by abnormal lipid accumulation. Celastrol is a pentacyclic triterpene extracted from Tripterygium wilfordii Hook F with anti-cancer activity. In the present study, the anticancer effects of celastrol on ccRCC and the underlying mechanisms were studied. Patients with reduced high density lipoprotein (HDL) and elevated levels of triglyceride (TG), total cholesterol (TC), low density lipoprotein (LDL) was found to have higher risk of ccRCC. In ccRCC clinical samples and cell lines, caveolin-1 (CAV-1) was highly expressed. CAV-1 was identified as a potential prognostic biomarker for ccRCC. Celastrol inhibited tumor growth and decreased lipid deposition promoted by high-fat diet . Celastrol reduced lipid accumulation and caveolae abundance, inhibited the binding of CAV-1 and lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) in ccRCC cells. Furthermore, celastrol attenuated stemness through blocking Wnt/β-catenin pathway after knockdown of CAV-1 and LOX-1. Therefore, the findings suggest that celastrol may be a promising active ingredient from traditional Chinese medicine for anti-cancer therapy.

摘要

透明细胞肾细胞癌（ccRCC）的特征是脂质异常蓄积。雷公藤红素是从雷公藤中提取的一种具有抗癌活性的五环三萜。在本研究中，研究了雷公藤红素对ccRCC的抗癌作用及其潜在机制。发现高密度脂蛋白（HDL）降低、甘油三酯（TG）、总胆固醇（TC）、低密度脂蛋白（LDL）水平升高的患者患ccRCC的风险更高。在ccRCC临床样本和细胞系中，小窝蛋白-1（CAV-1）高表达。CAV-1被确定为ccRCC的潜在预后生物标志物。雷公藤红素抑制肿瘤生长，并减少高脂饮食促进的脂质沉积。雷公藤红素减少脂质蓄积和小窝丰度，抑制ccRCC细胞中CAV-1与凝集素样氧化低密度脂蛋白受体-1（LOX-1）的结合。此外，在敲低CAV-1和LOX-1后，雷公藤红素通过阻断Wnt/β-连环蛋白通路减弱干性。因此，这些发现表明雷公藤红素可能是一种有前景的来自中药的抗癌治疗活性成分。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee87/8085775/d857b6b4cac7/fphar-12-658092-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee87/8085775/3677abb9e087/fphar-12-658092-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee87/8085775/83ebacbff020/fphar-12-658092-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee87/8085775/8b6c8ec1cffb/fphar-12-658092-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee87/8085775/858da9f12a51/fphar-12-658092-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee87/8085775/d857b6b4cac7/fphar-12-658092-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee87/8085775/3677abb9e087/fphar-12-658092-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee87/8085775/5dd4204c6ae6/fphar-12-658092-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee87/8085775/d869b6176629/fphar-12-658092-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee87/8085775/5a3d44707640/fphar-12-658092-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee87/8085775/83ebacbff020/fphar-12-658092-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee87/8085775/8b6c8ec1cffb/fphar-12-658092-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee87/8085775/858da9f12a51/fphar-12-658092-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee87/8085775/d857b6b4cac7/fphar-12-658092-g008.jpg

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