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作 者:林浩 代伟宏 刘昌江 陈宗军 严容燕 王先薇 LIN Hao;DAI Wei-hong;LIU Chang-jiang;CHEN Zong-jun;YAN Rong-yan;WANG Xian-wei(The Second Affiliated Hospital of Hainan Medical University,Haikou 570311,China)
出 处:《天然产物研究与开发》2023年第5期741-749,共9页Natural Product Research and Development
基 金:海南省卫生计生行业科研项目(22A200083,20A200 212)。
摘 要:本文旨在研究黄芩苷调控Hedgehog信号通路抗炎性结直肠癌的机制。不同剂量黄芩苷给予结直肠癌SW620细胞和结直肠癌AOM/DSS小鼠,采用MTT法、Hoechst33342/PI双染法、ELISA、RT-qPCR以及Western blot等多种技术进行检测。结果显示,黄芩苷能够明显抑制SW620细胞增殖且在高剂量和长时间培养情况下对NCM460细胞具有一定抑制作用,同时伴随Caspase-9和Caspase-3活性的增加。此外,黄芩苷抑制细胞IL-1β、IL-6和TNF-α的表达,降低Hedgehog信号通路SHH、SMO以及Gli1相关mRNA和蛋白的表达水平,同时提高SUFU mRNA和蛋白的表达水平。在AOM/DSS结直肠癌小鼠中,黄芩苷降低组织IL-1β、IL-6和TNF-α的表达,同时抑制Hedgehog信号通路SHH、SMO以及Gli1相关蛋白的表达水平,提高SUFU蛋白的表达水平。上述结果提示,黄芩苷能够抑制SW620细胞的增殖、克隆以及诱导细胞凋亡,同时降低细胞和组织中炎症因子的表达水平,其机制可能涉及对于Hedgehog信号通路的抑制。To research the mechanism of baicalin regulating the Hedgehog signal pathway against colitis-associated colorectal cancer.Different dosages of baicalin were given to colorectal cancer SW620 cells and colorectal cancer AOM/DSS mice.MTT,Hoechst33342/PI staining,ELISA,RT-qPCR,Western blot and other technologies were used for detection.The results authenticated that baicalin could significantly inhibit the proliferation of SW620 cells and demonstrate certain inhibitory effect on NCM460 cells under high dose and long-term,accompanied by an increase in the activities of Caspase-9 and Caspase-3.In addition,baicalin could inhibit the expression of IL-1β,IL-6 and TNF-αof cell,restrain the expressions of SHH,SMO and Gli1 mRNA and proteins in Hedgehog signal pathway,and increase the expression of SUFU mRNA and proteins.In the AOM/DSS colorectal cancer mouse,baicalin could inhibit the expression of IL-1β,IL-6 and TNF-αin tissues,reduce the expressions of SHH,SMO and Gli1 proteins in Hedgehog signal pathway,and enhance the expression of SUFU protein.The above results point out that,baicalin could inhibit the proliferation,cloning and apoptosis of human colorectal cancer SW620 cells,and reduce the expression of inflammatory factors in cells and tissues,which the mechanism may involve in the inhibition of Hedgehog signal pathway.
关 键 词:黄芩苷 结直肠癌 炎症 HEDGEHOG信号通路 凋亡
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