Effects of liquor-saturated process on the Stellera chamaejasmes anti-tumor activity and toxicity

doi:10.3969/j.issn.1000-1565.2020.04.009

Abstract

Abstract: The difference in anti-tumor activity and toxic reaction in vivo between the crude medicine and liquor-saturated products was compared, and its preliminary anti-tumor mechanism was studied. Intragastric administration was used to compare and study the inhibitory effects of different concentrations of liquor-saturated and crude of Stellera chamaejasme. solution on mices subcutaneous S180 tumor. Immunohistochemical method was used to detect the expression levels of Ki-67 and Caspase-3 in tumor tissues, and to explore the antitumor mechanism of the drugs. There was a significant difference in tumor inhibition between liquor-saturated group and the crude drug group(P<0.05). Compared with the blank control group, the spleen index and thymus index of the wine group were not statistically difference(P<0.05). liquor-saturated Stellera chamaejasme can significantly down-regulate Ki-67 expression in tumor tissue of S180 tumor-bearing mice(P<0.01), and can significantly up-regulate the expression of Caspase-3(P<0.01). Liquor-saturated process can enhance the Stellera Chamaejasmes anti-tumor activity in S180 transplanted mice, and reduce the Stellera chamaejasmes impact on spleen index of mice. The anti-tumor- DOI:10.3969/j.issn.1000-1565.2020.04.009酒制对瑞香狼毒抗肿瘤活性及毒性反应的影响李红玲¹,宋美燕¹,马昊然¹,陆艺蓓¹,马晓莉²,徐艳娇¹(1. 河北大学医学院,河北保定 071000;2.河北大学中医学院,河北保定 071000)摘要:实验对比了瑞香狼毒(stellera chamaejasme)生药和酒制品的体内抑瘤活性及毒性反应差异,并对其抑瘤机制进行了初步探讨.以灌胃的给药方式,对比不同浓度的酒制及生药瑞香狼毒溶液对小鼠S180皮下移植瘤的抑制作用.采用免疫组化法检测肿瘤组织Ki-67、Caspase-3的表达水平,探讨药物的抑瘤作用机制.结果表明:酒制瑞香狼毒组与生药组相比,抑瘤率有显著性差异(P<0.05);与空白对照组相比,酒制组脾指数、胸腺指数无统计学差异(P>0.05);酒制瑞香狼毒组S180荷瘤小鼠肿瘤组织中的Ki-67的表达显著下降(P<0.01),Caspase-3的表达增强(P<0.01).因此,酒制能增强瑞香狼毒对S180荷瘤小鼠的抑瘤活性,同时能减轻生药对小鼠脾指数的影响;其抗肿瘤作用机制可能与S180细胞中Ki-67的表达下降以抑制其增殖,Caspase-3的表达增强以促进细胞凋亡有关.关键词:瑞香狼毒;酒制;Ki-67;Caspase-3中图分类号:R332 文献标志码:A 【additional_page=420】文章编号:1000-1565(2020)04-0392-07Effects of liquor-saturated process on the Stellera chamaejasmes anti-tumor activity and toxicity LI Hongling¹, SONG Meiyan¹, MA Haoran¹, LU Yibei¹, MA Xiaoli², XU Yanjiao¹(1.Medical College,Hebei University,Baoding 071000,China;2.College of Traditional Chinese Medicine,Hebei University,Baoding 071000,China)Abstract: The difference in anti-tumor activity and toxic reaction in vivo between the crude medicine and liquor-saturated products was compared, and its preliminary anti-tumor mechanism was studied. Intragastric administration was used to compare and study the inhibitory effects of different concentrations of liquor-saturated and crude of Stellera chamaejasme. solution on mices subcutaneous S180 tumor. Immunohistochemical method was used to detect the expression levels of Ki-67 and Caspase-3 in tumor tissues, and to explore the antitumor mechanism of the drugs. There was a significant difference in tumor inhibition between liquor-saturated group and the crude drug group(P<0.05). Compared with the blank control group, the spleen index and thymus index of the wine group were not statistically difference(P<0.05). liquor-saturated Stellera chamaejasme can significantly down-regulate Ki-67 expression in tumor tissue of S180 tumor-bearing mice(P<0.01), and can significantly up-regulate the expression of Caspase-3(P<0.01). Liquor-saturated process can enhance the Stellera Chamaejasmes anti-tumor activity in S180 transplanted mice, and reduce the Stellera chamaejasmes impact on spleen index of mice. The anti-tumor- 收稿日期:2019-11-10 基金项目:河北省科技厅资助项目(17272502D) 第一作者:李红玲(1978—),女,河北容城人,河北大学实验师,主要从事中药抗肿瘤研究.E-mail:980374832@qq.com 通信作者:马晓莉(1967—),女,河北定兴人,河北大学教授,主要从事中药药物分析方向研究.E-mail:ma_ xiaoli@163.com第4期李红玲等:酒制对瑞香狼毒抗肿瘤活性及毒性反应的影响mechanism may be related to down-regulation of Ki-67 expression and enhancement of Caspase-3 expression. liquor-saturated Stellera chamaejasme can inhibit the proliferation of S180 tumor cells and promote their apoptosis.

Key words: Stellera chamaejasme, liquor-saturated, Ki-67, Caspase-3

CLC Number:

R332

LI Hongling, SONG Meiyan, MA Haoran, LU Yibei, MA Xiaoli, XU Yanjiao. Effects of liquor-saturated process on the Stellera chamaejasmes anti-tumor activity and toxicity[J]. Journal of Hebei University (Natural Science Edition), 2020, 40(4): 392-398.

References

[1] 李时珍.本草纲目[M].北京:人民卫生出版社,1982:1126.
[2] 陶弘景.本草经集注[M].北京:人民卫生出版社,1994:342.
[3] 冯宝民,裴月湖,张海龙,等.瑞香狼毒中的化学成分[J].中草药,2004(1): 16-18.DOI:10.3321/j.issn:0253-2670.2004.01.004.
[4] 沈佳钰.瑞香狼毒药理活性研究进展[J].内蒙古中医药,2017, 36(8): 151-152.DOI:10.16040/j.cnki.cn15-1101.2017.08.145.
[5] 吴宏辉,李红丽,王文全,等.瑞香狼毒抗癌作用研究进展[J].中国中医药信息杂志,2016, 23(11): 127-130. DOI:10.3969/j.issn.1005-5304.2016.11.034.
[6] 胡蓉蓉,王义善.瑞香狼毒抗肿瘤作用研究进展[J].人民军医,2010, 53(2): 151-152.
[7] 宋海平,任韶韶,肖超,等.瑞香狼毒抗肿瘤作用机制研究进展[J].山东医药,2016, 56(21): 98-101.DOI:10.3969/j.issn.1002.266X.2016.21.040.
[8] 陈丽霞,任连生,杨永明, 等.瑞香狼毒水提醇沉物对H22荷瘤小鼠抑瘤作用研究[J].中国药物与临床,2017, 17(4): 489-491.DOI:10.11655/zgywylc2017.04.008.
[9] 韩波,屈萌,马晓莉,等.狼毒毒性和炮制方法研究进展[J].中药材,2013, 36(2): 330-333.DOI:10.13863/j.issn1001-4454.2013.02.046.
[10] 潘国凤,杨庆,刘安,等.瑞香狼毒药效组分抑制小鼠皮下移植瘤H22的实验研究[J].中华中医药杂志,2009, 24(4): 438-442.
[11] 王芦笛. 基于液质联用技术的瑞香狼毒化学成分及药代动力学研究[D].保定:河北大学,2017:40-50.
[12] 李红玲,陆艺蓓,马昊然,等.细胞凋亡检测技术在瑞香狼毒抗肿瘤研究中的应用[J].医学研究与教育,2019, 36(1): 1-5.DOI:10.3969/j.issn.1674-490X.2019.01.001.
[13] BERGIN I L,SMEDLEY R C,ESPLIN D G,et al.Prognostic evaluation of Ki67 threshold value in canine iral melanoma[J].Veterinary Pathology,2011,48:41-53.
[14] ASHRAFUL HOQUE, DAVID G.MENTER, AYSEGUL A SAHIN, et al. No increased Ki67 expression in ductal carcinoma in situ associated with invasive breast cancer [J]. Cancer Epidemiol Biomarkers Prev, 2001,10:153-154.
[15] KERR J F,WYLLIE A H,CURRIE A R.Apoptosis:a basic biological phenomenon with wide-ranging implications in tissue kinetics[J].Brit J Cancer,1972,26:239-257.
[16] MARTINCZ M,REIF RD,PAPPAS D,et a1.Early detection of apoptosisin living cells by fluoreascence correlation spectroscopy[J].Analytical and Bioanalytical Chemistry,2010,396:1177-1185.