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蜂王酸(10-羟基-2-癸烯酸)单独及与环磷酰胺联合应用的抗肿瘤作用及其对艾氏腹水癌小鼠的细胞机制。

Anti-Tumor Effects of Queen Bee Acid (10-Hydroxy-2-Decenoic Acid) Alone and in Combination with Cyclophosphamide and Its Cellular Mechanisms against Ehrlich Solid Tumor in Mice.

机构信息

Department of Biology, Faculty of Science, University of Tabuk, Tabuk 71491, Saudi Arabia.

Department of Biology, College of Science and Humanities-Al Quwaiiyah, Shaqra University, Al Quwaiiyah 19257, Saudi Arabia.

出版信息

Molecules. 2021 Nov 20;26(22):7021. doi: 10.3390/molecules26227021.

Abstract

Queen bee acid or 10-hydroxy-2-decenoic acid (10-HDA) is one of the main and unique lipid components (fatty acids) in royal jelly. Previous studies have demonstrated that 10-HDA has various pharmacological and biological activities. The present study aims to evaluate the anti-tumor effects of 10-HDA alone and combined with cyclophosphamide (CP), as an alkylating agent which widely used for the treatment of neoplastic cancers, against the Ehrlich solid tumors (EST) in mice. Methods: A total of 72 female Swiss albino mice were divided into eight groups. EST mice were treated with 10-HDA (2.5 and 5 mg/kg) alone and combined with CP (25 mg/kg) orally once a day for 2 weeks. Tumor growth inhibition, body weight, the serum level of alpha-fetoprotein (AFP) and carcinoembryonic antigen tumor (CAE), liver and kidney enzymes, tumor lipid peroxidation (LPO) and nitric oxide (NO), antioxidant enzymes (e.g. glutathione reductase (GR), glutathione peroxidase (GPx), catalase enzyme (CAT)), tumor necrosis factor alpha level (TNF-α), and the apoptosis-regulatory genes expression were assessed in tested mice. Results: the findings exhibited that treatment of EST-suffering mice with 10-HDA at the doses of 2.5 and 5 mg/kg especially in combination with CP significantly ( < 0.001) decreased the tumor volume and inhibition rate, tumor markers (AFP and CEA), serum level of liver and kidney, LPO and NO, TNF-α level, as well as the expression level of Bcl-2 in comparison with the mice in the C2 group; while 10-HDA at the doses of 2.5 and 5 mg/kg especially in combination with CP significantly ( < 0.001) improved the level of antioxidant enzymes of GPx, CAT, and SOD and the expression level of caspase-3 and Bax genes. : According to the results of the present investigations, 10-HDA at the doses of 2.5 and 5 mg/kg especially in combination with CP showed promising antitumor effects against EST in mice and can be recommended as a new or alternative anticancer agent against tumor; nevertheless, further investigations, particularly in clinical setting, are required to confirm these results.

摘要

蜂王酸或 10-羟基-2-癸烯酸(10-HDA)是蜂王浆中主要的独特脂质成分(脂肪酸)之一。先前的研究表明,10-HDA 具有多种药理和生物学活性。本研究旨在评估 10-HDA 单独使用以及与环磷酰胺(CP)联合使用(作为广泛用于治疗肿瘤癌症的烷化剂)对小鼠艾氏腹水瘤(EST)的抗肿瘤作用。方法:将 72 只雌性瑞士白化小鼠分为 8 组。EST 小鼠每天口服给予 10-HDA(2.5 和 5mg/kg)单独或联合 CP(25mg/kg)一次,连续 2 周。评估受试小鼠的肿瘤生长抑制率、体重、血清甲胎蛋白(AFP)和癌胚抗原肿瘤(CAE)水平、肝肾功能酶、肿瘤脂质过氧化(LPO)和一氧化氮(NO)、抗氧化酶(如谷胱甘肽还原酶(GR)、谷胱甘肽过氧化物酶(GPx)、过氧化氢酶(CAT))、肿瘤坏死因子α水平(TNF-α)以及凋亡调控基因表达。结果:结果表明,用 2.5 和 5mg/kg 剂量的 10-HDA 特别是联合 CP 治疗 EST 患病小鼠,与 C2 组小鼠相比,显著(<0.001)降低了肿瘤体积和抑制率、肿瘤标志物(AFP 和 CEA)、血清肝肾功能、LPO 和 NO、TNF-α 水平以及 Bcl-2 的表达水平;而 2.5 和 5mg/kg 剂量的 10-HDA 特别是联合 CP 显著(<0.001)提高了 GPx、CAT 和 SOD 的抗氧化酶水平以及 caspase-3 和 Bax 基因的表达水平。结论:根据本研究的结果,2.5 和 5mg/kg 剂量的 10-HDA 特别是联合 CP 对 EST 小鼠具有显著的抗肿瘤作用,可以推荐作为一种新的或替代的抗肿瘤药物;然而,需要进一步的研究,特别是在临床环境中,以确认这些结果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e91/8617861/19d229a35d26/molecules-26-07021-g001.jpg

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