黑根霉胞外多糖联合奥沙利铂对二甲肼诱导的大鼠结肠癌的抑制作用及对Survivin/caspase-3/caspase-7的影响  

Inhibitory effect of exopolysaccharide from Rhizopus nigricans combined with oxaliplatin on dimethylhydrazine-induced colon cancer in rats and its effect on Survivin/caspase-3/caspase-7

作　　者：王颜天池 鹿艳 韩军 王国栋 袁平川 柳春燕 陈靠山 WANGYAN Tian-chi;LU Yan;HAN Jun;WANG Guo-dong;YUAN Ping-chuan;LIU Chun-yan;CHEN Kao-shan(Anhui Provincial Engineering Research Center for Polysaccharide Drugs,Anhui Province Key Lab of Active BiologicalMacromolecules,Drug Research & Development Center,School of Pharmacy,Wannan Medical College,Wuhu Anhui241002,China;School of Life Sciences,Shandong University,Qingdao Shandong266000,China)

机构地区：[1]安徽省多糖药物工程技术研究中心活性生物大分子研究安徽省重点实验室皖南医学院药物研发中心皖南医学院药学院,安徽芜湖241002 [2]山东大学生命科学学院,山东青岛266000

出　　处：《中国药理学通报》2019年第5期690-694,共5页Chinese Pharmacological Bulletin

基　　金：安徽高校自然科学研究重大项目(No KJ2018ZD025);活性生物大分子研究安徽省重点实验室自主研究课题(No LAB201801)

摘　　要：目的研究黑根霉胞外多糖(exopolysaccharide from Rhizopus nigricans,EPS)联合奥沙利铂对大鼠结肠癌的抑制作用及其作用机制。方法采用皮下注射1,2-二甲肼(DMH)建立大鼠结肠癌模型。将实验大鼠随机分为空白对照组、模型组、EPS组(150 mg·kg^(-1))、奥沙利铂组(10 mg·kg^(-1))和EPS+奥沙利铂组。HE染色观察大鼠结肠组织的病理学变化; Western blot和免疫组化法检测大鼠结肠组织中Survivin、caspase-3和caspase-7的蛋白表达变化。结果HE染色结果可见,治疗组可以明显改善结肠组织的损伤程度。与模型组相比,治疗组中Survivin蛋白的表达下降,caspase-3、caspase-7蛋白的表达上升,差异有统计学意义(P<0. 05)。结论 EPS和奥沙利铂都具有抑制大鼠结肠癌的作用,且协同效果更明显。其作用机制可能是通过抑制Survivin蛋白的表达,升高caspase-3和caspase-7蛋白的表达,从而促进肿瘤细胞的凋亡,抑制了肿瘤的发生和发展。Aim To study the inhibitory effect of exopolysaccharide from Rhizopus nigricans (EPS) combined with oxaliplatin on colon cancer in rats and its mechanism. Methods Colon cancer model in rats was established by subcutaneous injection of 1,2-dimethylhydrazine (DMH).The experimental rats were randomly divided into five groups:control group,model group,EPS group (150 mg·kg-1 ),oxaliplatin group (10 mg·kg-1 ) and EPS+oxaliplatin group.The histopathological changes of colon tissues in rats were observed by HE staining.The expression levels of Survivin,caspase-3 and caspase-7 proteins in colon tissues were detected by Western blot and immunohistochemistry. Results HE staining results showed that the damage degree of colon tissues could be significantly improved in treatment groups.Compared with model group,the expression of Survivin protein in treatment groups decreased significantly,and the expression of caspase-3 and caspase-7 proteins increased ( P <0.05). Conclusions Both EPS and oxaliplatin inhibit colon cancer in rats,and the synergistic effect is more remarkable.Its mechanism may be through inhibiting the expression of Survivin protein and increasing the expression of caspase-3 and caspase-7 proteins,thereby promoting the apoptosis of tumor cells and inhibiting the occurrence and development of tumors.

关 键 词：胞外多糖 黑根霉 奥沙利铂 结肠癌 SURVIVIN CASPASE-3 CASPASE-7 

分 类 号：R-332[医药卫生] R284.1