摘要
目的:探讨迷迭香酸对肝癌移植瘤的抑制作用及其诱导凋亡机制。方法:采用肝癌H22荷瘤小鼠模型,按分层随机方法分为正常对照组、模型组、环磷酰胺组(CTX,20 mg·kg^-1),迷迭香酸低、中、高剂量(75 mg·kg^-1,150 mg·kg^-1,300 mg·kg^-1)组,每组8只,各给药组连续给药10 d,观察各组小鼠的肿瘤生长情况,计算抑瘤率。苏木精-伊红(HE)染色观察肿瘤组织病理学改变,Western blot检测肿瘤组织中信号传导与转录激活因子(STAT3)和p38促分裂原活化蛋白激酶(MAPK)的表达,免疫组织化学法和实时荧光定量聚合酶链反应(qPCR)检测肿瘤组织Caspase-3的表达。结果:与模型组相比,迷迭香酸各剂量组的瘤重均有明显下降(P<0.05),且能不同程度的促进肿瘤细胞坏死,降低肿瘤细胞数。迷迭香酸各剂量组均能有效降低荷瘤小鼠肿瘤组织中STAT3蛋白的表达,迷迭香酸中剂量组能显著升高p38磷酸化水平(P<0.05),迷迭香酸高剂量组能显著升高肿瘤组织中Caspase-3蛋白和mRNA的表达。结论:迷迭香酸能够抑制荷瘤小鼠肿瘤的生长,其机制可能与调节STAT3和p38 MAPK信号通路,促进Caspase-3的表达有关。
Objective:To investigate the anti-tumor effect and the mechanism of inducing apoptosis of rosmarinic acid on liver cancer xenografts.Methods:Liver cancer H22 tumor-bearing mice models were created and randomly divided into normal control group,model group,cyclophosphamide group(CTX,20 mg·kg^-1),and low,medium and high doses of rosmarinic acid(75 mg·kg^-1,150 mg·kg^-1,and 300 mg·kg^-1)groups,with 8 mice in each group.Mice in each group were administered for 10 consecutive days,the tumor growth was observed,and the tumor suppression rate was calculated.HE staining was used to observe the pathological changes of tumor tissues.Western blot was employed to detect the expression of signal transducers and activators of transcription(STAT3)and p38 mitogen-activated protein kinases(MAPK)in tumor tissues.Immunohistochemistry and real-time fluorescent quantitative polymerase chain reaction(qPCR)were used to detect the expression of Caspase-3 in tumor tissues.Results:Compared with the model group,the tumor weight decreased significantly in each dose group of rosmarinic acid(P<0.05),and it promoted tumor cell necrosis and reduced the number of tumor cells in varying degrees.The expression of STAT3 protein in tumor tissues of tumor-bearing mice was reduced in each dose group of rosmarinic acid,the phosphorylation level of p38 in the medium dose group was significantly increased(P<0.05),and the expression of Caspase-3 protein and mRNA were significantly increased in the high dose group.Conclusion:Rosmarinic acid can inhibit tumor growth in tumor-bearing mice,and the mechanism may be related to the regulation of STAT3 and p38 MAPK signaling pathways and promotion of Caspase-3 expression.
作者
曹雯
韦斯军
张文娟
莫凯
蒋伟哲
Cao Wen;Wei Sijun;Zhang Wenjuan;Mo Kai;Jiang Weizhe(Department of Pharmacy,Guangxi International Zhuang Medicine Hospital,Nanning 530200,China;Department of Pharmacy,the Fifth Affiliated Hospital of Guangxi Medical University,Nanning 530022,China;Pharmaceutical College Guangxi Medical University,Nanning 530021,China)
出处
《广西医科大学学报》
CAS
2020年第3期405-410,共6页
Journal of Guangxi Medical University
基金
广西中医药大学博士科研启动基金项目(No.2017BS047)
广西卫健委自筹经费科研课题资助项目(No.Z20190316)
广西创新驱动发展专项课题资助项目(No.桂科AA17202050)。
关键词
迷迭香酸
肝癌
抗肿瘤
凋亡
rosmarinic acid
liver cancer
anticancer
apoptosis
