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塞内加尔番荔枝提取物在雄性 Wistar 大鼠二乙基亚硝胺诱导的肝癌中表现出抗癌特性。

Annona senegalensis extract demonstrates anticancer properties in N-diethylnitrosamine-induced hepatocellular carcinoma in male Wistar rats.

机构信息

Department of Biochemistry, College of Science and Technology, Covenant University, Canaan Land, Ota PMB 1023, Ogun State, Nigeria.

Department of Biochemistry, Adekunle Ajasin University, Akungba-Akoko, Ondo State, Nigeria.

出版信息

Biomed Pharmacother. 2020 Nov;131:110786. doi: 10.1016/j.biopha.2020.110786. Epub 2020 Sep 30.

Abstract

BACKGROUND

Hepatocellular carcinoma (HCC) is a common and leading cancer around the globe. This study investigated the anticancer properties of extract of Annona senegalensis in N-diethylnitrosamine (DEN) - induced hepatocellular carcinoma in male Wistar rats.

METHODS

Rats were simultaneously induced with a combination of 100 mg/kg b.wt of DEN and 0.5 mL/kg of carbon tetrachloride (CCl) intraperitoneally once a week for three weeks in a row. Thereafter, animals were treated with 100 mg/kg and 200 mg/kg b.wt of A. senegalensis extract daily for 21days. Analysis using gas chromatography-mass spectrometry (GC-MS) was carried out to discover the phytoconstituents contained in the n-hexane extract of A. senegelensis. The levels of liver function parameters and antioxidant enzyme activities were determined via spectrophotometric analysis. Reverse transcriptase-polymerase chain reaction technique was used to assess the gene expression patterns of BCL-2, P53, P21, IL-6, FNTA, VEGF, HIF, AFP, XIAP, and EGFR mRNAs.

RESULTS

Treatment of DEN-induced hepatocellular carcinoma Wistar rats with the extract caused significant (p < 0.05) decrease in the activities of ALT and AST. It also resulted in a reduction of the concentration of MDA and a significant increase (p < 0.05) in SOD and GSH activities. IL-6, BCL-2, VEGF, EGFR, XIAP, FNTA, and P21 mRNAs expressions were significantly (p < 0.05) downregulated after treatment. Histopathological analysis revealed that the extract improved the liver architecture.

CONCLUSION

A. senegelensis n-hexane extract demonstrates its anticancer properties by improving the liver architecture, increasing the antioxidant defense systems, downregulating the pro-inflammatory, anti-apoptotic, angiogenic, alpha-fetoprotein and farnesyl transferase mRNAs expression and hitherto up-regulate the expression of tumor suppressor (P21 and P53) mRNAs.

摘要

背景

肝细胞癌(HCC)是全球常见且主要的癌症。本研究探讨了番荔枝提取物在二乙基亚硝胺(DEN)诱导的雄性 Wistar 大鼠肝细胞癌中的抗癌特性。

方法

大鼠同时每周一次腹膜内注射 100mg/kg b.wt 的 DEN 和 0.5mL/kg 的四氯化碳(CCl),连续三周。此后,动物每天接受 100mg/kg 和 200mg/kg b.wt 的 A. senegalensis 提取物治疗 21 天。使用气相色谱-质谱联用仪(GC-MS)分析以发现番荔枝 n-己烷提取物中所含的植物成分。通过分光光度分析测定肝功能参数和抗氧化酶活性水平。使用逆转录-聚合酶链反应技术评估 BCL-2、P53、P21、IL-6、FNTA、VEGF、HIF、AFP、XIAP 和 EGFR mRNA 的基因表达模式。

结果

用提取物治疗 DEN 诱导的肝细胞癌 Wistar 大鼠导致 ALT 和 AST 活性显著(p<0.05)降低。它还导致 MDA 浓度降低,SOD 和 GSH 活性显著增加(p<0.05)。治疗后,IL-6、BCL-2、VEGF、EGFR、XIAP、FNTA 和 P21 mRNA 的表达均显著(p<0.05)下调。组织病理学分析显示,提取物改善了肝结构。

结论

番荔枝 n-己烷提取物通过改善肝结构、增加抗氧化防御系统、下调促炎、抗凋亡、血管生成、甲胎蛋白和法呢基转移酶 mRNA 的表达,以及迄今为止上调肿瘤抑制基因(P21 和 P53)mRNA 的表达,显示其抗癌特性。

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