人参倍半萜有效部位对S180荷瘤小鼠的抗肿瘤活性及其作用机制

doi:10.13481/j.1671-587x.20190212

吉林大学学报(医学版) ›› 2019, Vol. 45 ›› Issue (02): 280-285.doi: 10.13481/j.1671-587x.20190212

• 基础研究 • 上一篇

人参倍半萜有效部位对S₁₈₀荷瘤小鼠的抗肿瘤活性及其作用机制

张静¹, 赵岩¹, 蔡恩博¹, 祝洪艳¹, 李平亚², 刘金平²

1. 吉林农业大学中药材学院中药学系中药化学教研室, 吉林长春 130118;
2. 吉林大学药学院新药研究室, 吉林长春, 130021

收稿日期:2018-06-29 发布日期:2019-03-29
通讯作者: 赵岩,教授,硕士研究生导师(Tel:0431-84533358,E-mail:zhyjlu79@163.com);刘金平,教授,博士研究生导师(Tel:0431-85619803,E-mail:liujp@jlu.edu.cn) E-mail:zhyjlu79@163.com;liujp@jlu.edu.cn
作者简介:张静(1991-),女,河南省鹤壁市人,在读医学硕士,主要从事天然药物化学成分与生物活性方面的研究。
基金资助:
国家科技部重点研发计划项目资助课题（2016YFC0500303）；吉林省科技厅科技发展计划项目资助课题（20150307012YY）

Anti-tumor activity of sesquiterpenoids from ginseng in S₁₈₀tumor-bearing mice and its mechanism

ZHANG Jing¹, ZHAO Yan¹, CAI Enbo¹, ZHU Hongyan¹, LI Pingya², LIU Jinping²

1. Chinese Medicine Chemistry Laboratory, Department of Traditional Chinese Medicine, College of Chinese Herbal Medicine, Jilin Agricultural University, Changchun 130118, China;
2. New Drug Research Laboratory, School of Pharmacy, Jilin University, Changchun 130021, China

Received:2018-06-29 Published:2019-03-29

摘要/Abstract

摘要： 目的：探讨人参倍半萜有效部位（SPG）对S₁₈₀荷瘤小鼠的体内抗肿瘤活性，并阐明其作用机制。方法：以ICR级雄性小鼠建立S₁₈₀荷瘤小鼠模型，将成模荷瘤小鼠分为模型组、5-氟尿嘧啶（5-FU）组（20 mg·kg^-1，ip）、低剂量SPG组（2.5 mg·kg^-1，ig）和高剂量SPG组（10 mg·kg^-1，ig），每组8只；另取8只ICR级雄性小鼠作为空白对照组。分别给药14d后，小鼠眼球取血后脱臼处死，剥离肿瘤组织并称质量，计算抑瘤率。测定各组小鼠血清中丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）、血尿素氮（BUN）、白细胞介素2（IL-2）、肿瘤坏死因子α（TNF-α）和血管内皮生长因子（VEGF）水平，HE染色观察各组小鼠肿瘤组织形态表现，采用Western blotting法检测肿瘤组织中抗细胞凋亡因子Bcl-2、VEGF、p38对丝裂原活化蛋白激酶（p38MAPK）和p-p38对丝裂原活化蛋白激酶（p-p38MAPK）蛋白表达水平。结果：随着SPG剂量的升高，SPG组小鼠抑瘤率明显升高，高剂量SPG组小鼠抑瘤率可达76.29%。与模型组比较，低和高剂量SPG组小鼠血清中IL-2和TNF-α水平明显升高（P<0.01），ALT、AST、BUN和VEGF水平明显降低（P<0.05或P<0.01）。HE染色，模型组小鼠肿瘤组织细胞排列整齐紧密，可见大量细胞核，且生长状态良好；低和高剂量SPG组小鼠肿瘤组织细胞核数量明显减少，排列松散，出现大面积坏死区域。Western blotting法检测，与模型组比较，低和高剂量SPG组小鼠肿瘤组织中Bcl-2和VEGF蛋白表达水平明显降低（P<0.01），p-p38MAPK蛋白表达水平明显升高（P<0.01）。结论：SPG对S₁₈₀荷瘤小鼠具有良好的抗肿瘤作用，其作用机制可能与降低Bcl-2和VEGF表达及激活p38MAPK蛋白通道有关。

关键词: 人参倍半萜, 抗肿瘤活性, 5-氟尿嘧啶, S₁₈₀荷瘤小鼠

Abstract: Objective: To investigate the anti-tumor activity in vivo of sesquiterpenoids from ginseng (SPG) in the S₁₈₀ tumor-bearing mice, and to clarify its mechanism.Methods: The ICR male mice were used to establish the S₁₈₀ tumor-bearing models. The model mice were randomly divided into model group, 5-fluorouracil (5-FU) group (20 mg·kg^-1, ip), low dose of SPG group (2.5 mg·kg^-1, ig),and high dose of SPG group (10.0 mg·kg^-1, ig), 8 mice in each group;another 8 mice were selected and used as blank control group. Fourteen days after administration, the blood samples were collected from the eyes of all mice, and they were sacrificed by cervical dislocation, then the tumor tissue was excised and weighed;the inhibitory rate of tumor was calculated;the serum levels of alanine aminotransferase(AST), aspartate aminotransferase(ALT), urea nitrogen(BUN), interleukin-2(IL-2), tumor necrosis factor-α(TNF-α) and vascular endothelial growth factor (VEGF) of the mice in various groups were measured;the pathological changes of the tumor tissue of the mice in various groups were observed by HE staining;the expression levels of anti-apoptotic factor Bcl-2, VEGF, p38 against mitogen-activated protein kinase (p38MAPK) and p-p38 against mitogen-activated protein kinase (p-p38MAPK) in the tumor tissue of the mice in various groups were analyzed by Western blotting method.Results: The inhibitory rates of the mice in SPG groups were increased significantly as the increase of SPG dose, and the inhibitory rate of tumor of the mice in high dose of SPG group was 76.29%. Compared with model group, the serum levels of IL-2 and TNF-α of the mice in SPG groups were significantly increased (P<0.01) and the levels of ALT, AST, BUN and VEGF were significantly decreased (P<0.05 or P<0.01). The HE staining results showed that the cells in model group were arranged neatly, a large number of nuclei were observed and the growth state was good;in low and high doses of SPG group, the number of nuclei in the tumor tissue of the mice was significantly reduced, the arrangement was loose, and a large area of necrosis occurred.The Western blotting results showed that compared with model group, the expression levels of Bcl-2 and VEGF proteins were significantly decreased (P<0.01) and the expression levels of p-p38MAPK protein in low and high doses of SPG groups were significantly increased (P<0.01).Conclusion: SPG has a good anti-tumor effect in the S₁₈₀ tumor-bearing mice, and its mechanism may be associated with the decreasing of Bcl-2 and VEGF expressions and activation of p38 MAPK protein channel.

Key words: sesquiterpenoids from ginseng, anti-tumor activity, 5-fluorouracil, S₁₈₀ tumor-bearing mice

中图分类号:

R285.5

张静, 赵岩, 蔡恩博, 祝洪艳, 李平亚, 刘金平. 人参倍半萜有效部位对S₁₈₀荷瘤小鼠的抗肿瘤活性及其作用机制[J]. 吉林大学学报(医学版), 2019, 45(02): 280-285.

ZHANG Jing, ZHAO Yan, CAI Enbo, ZHU Hongyan, LI Pingya, LIU Jinping. Anti-tumor activity of sesquiterpenoids from ginseng in S₁₈₀tumor-bearing mice and its mechanism[J]. Journal of Jilin University(Medicine Edition), 2019, 45(02): 280-285.

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人参倍半萜有效部位对S₁₈₀荷瘤小鼠的抗肿瘤活性及其作用机制

Anti-tumor activity of sesquiterpenoids from ginseng in S₁₈₀tumor-bearing mice and its mechanism

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