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通过 p53 和细胞周期对小鼠鳞状细胞肺癌模型肺组织的白藜芦醇的化学预防作用。

Chemopreventive effects of pterostilbene through p53 and cell cycle in mouse lung of squamous cell carcinoma model.

机构信息

Programme of Biomedical Science, Center for Toxicology and Health Risk Studies (CORE), Faculty of Health Sciences, Universiti Kebangsaan Malaysia (UKM), Kuala Lumpur, Malaysia.

出版信息

Sci Rep. 2021 Jul 21;11(1):14862. doi: 10.1038/s41598-021-94508-7.

Abstract

Cell proliferation and cell death abnormalities are strongly linked to the development of cancer, including lung cancer. The purpose of this study was to investigate the effect of pterostilbene on cell proliferation and cell death via cell cycle arrest during the transition from G1 to S phase and the p53 pathway. A total of 24 female Balb/C mice were randomly categorized into four groups (n = 6): N-nitroso-tris-chloroethyl urea (NTCU) induced SCC of the lungs, vehicle control, low dose of 10 mg/kg PS + NTCU (PS10), and high dose of 50 mg/kg PS + NTCU (PS50). At week 26, all lungs were harvested for immunohistochemistry and Western blotting analysis. Ki-67 expression is significantly lower, while caspase-3 expression is significantly higher in PS10 and PS50 as compared to the NTCU (p < 0.05). There was a significant decrease in cyclin D1 and cyclin E2 protein expression in PS10 and PS50 when compared to the NTCU (p < 0.05). PS50 significantly increased p53, p21, and p27 protein expression when compared to NTCU (p < 0.05). Pterostilbene is a potential chemoprevention agent for lung SCC as it has the ability to upregulate the p53/p21 pathway, causing cell cycle arrest.

摘要

细胞增殖和细胞死亡异常与癌症的发展密切相关,包括肺癌。本研究旨在通过 G1 期到 S 期的细胞周期阻滞和 p53 通路探讨紫檀芪对细胞增殖和细胞死亡的影响。将 24 只雌性 Balb/C 小鼠随机分为四组(n = 6):N-亚硝基三氯乙基亚硝脲(NTCU)诱导的 SCC 肺、载体对照、低剂量 10mg/kg PS + NTCU(PS10)和高剂量 50mg/kg PS + NTCU(PS50)。在第 26 周,所有肺均用于免疫组织化学和 Western blot 分析。与 NTCU 相比,PS10 和 PS50 中的 Ki-67 表达明显降低,而 caspase-3 表达明显升高(p < 0.05)。与 NTCU 相比,PS10 和 PS50 中的细胞周期蛋白 D1 和细胞周期蛋白 E2 蛋白表达显著降低(p < 0.05)。与 NTCU 相比,PS50 显著增加了 p53、p21 和 p27 蛋白的表达(p < 0.05)。紫檀芪是一种潜在的肺癌 SCC 化学预防剂,因为它能够上调 p53/p21 通路,导致细胞周期阻滞。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa31/8295275/43a954aaa25e/41598_2021_94508_Fig1_HTML.jpg

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