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红参通过抑制p53介导的p21和p27上调,预防C57BL/6小鼠中尼拉帕尼诱导的骨髓抑制。

Red ginseng prevents niraparib-induced myelosuppression in C57BL/6 mice via inhibiting p53-mediated upregulation of p21 and p27.

作者信息

Liao Huiyan, Hu Xiangdan, Chen Shenming, Fan Zhaofeng, Xiao Jing

机构信息

Guangdong Provincial Key Laboratory of Major Obstetric Diseases, Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510140, People's Republic of China.

The Second Clinical College of Guangzhou, University of Chinese Medicine, Guangzhou, Guangdong, 510006, People's Republic of China.

出版信息

J Nat Med. 2025 Mar;79(2):381-390. doi: 10.1007/s11418-024-01866-3. Epub 2024 Dec 30.

Abstract

Myelosuppression is a serious and common complication of targeted therapy for cancer patients, and there are few studies exploring the efficacy of natural drugs in this condition. Niraparib is a widely used targeted therapy for the treatment of advanced ovarian cancer. As a poly (ADP-ribose) polymerase (PARP) inhibitor, niraparib significantly improves progression-free and overall survival in patients. We aimed to explore the potential effect of red ginseng (RG) on niraparib-induced myelosuppression and to further reveal its possible molecular mechanism. Female C57BL/6 mice were divided into control, tumor, model, and RG groups (n = 6). After receiving ID8 ovarian cancer cell inoculation, the mice received niraparib treatment (80 mg/kg) for 3 days. Meanwhile, RG groups (100 and 200 mg/kg) were intragastrically treated with RG extract for 7 days. Compared with the model group, RG extract increased the counts of peripheral blood cells and enhanced the hematopoietic function of bone marrow. Furthermore, RG extract increased the colony yield of hematopoietic progenitor cells (HPCs), facilitated DNA damage repair, alleviated the G0/G1 phase cell cycle arrest, and significantly reversed the increased expression levels of p53, p21, and p27, while stimulating cyclinE1 expression levels. These findings indicate that RG might have therapeutic potential on niraparib-induced myelosuppression, which encourages further clinical trials. This study is the first to explore the efficacy and mechanism of RG in preventing myelosuppression induced by niraparib.

摘要

骨髓抑制是癌症患者靶向治疗的一种严重且常见的并发症,而探索天然药物在此情况下疗效的研究较少。尼拉帕利是一种广泛用于治疗晚期卵巢癌的靶向治疗药物。作为一种聚(ADP - 核糖)聚合酶(PARP)抑制剂,尼拉帕利可显著提高患者的无进展生存期和总生存期。我们旨在探讨红参(RG)对尼拉帕利诱导的骨髓抑制的潜在作用,并进一步揭示其可能的分子机制。将雌性C57BL/6小鼠分为对照组、肿瘤组、模型组和RG组(n = 6)。接种ID8卵巢癌细胞后,小鼠接受尼拉帕利治疗(80 mg/kg)3天。同时,RG组(100和200 mg/kg)用RG提取物灌胃治疗7天。与模型组相比,RG提取物增加了外周血细胞计数,增强了骨髓造血功能。此外,RG提取物增加了造血祖细胞(HPC)的集落产量,促进了DNA损伤修复,减轻了G0/G1期细胞周期阻滞,并显著逆转了p53、p21和p27表达水平的升高,同时刺激了细胞周期蛋白E1的表达水平。这些发现表明,RG可能对尼拉帕利诱导的骨髓抑制具有治疗潜力,这鼓励进一步开展临床试验。本研究首次探讨了RG预防尼拉帕利诱导的骨髓抑制的疗效和机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eaa2/11880060/ac6bfb526d78/11418_2024_1866_Fig1_HTML.jpg

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