红景天苷通过抑制STAT3活化调控结肠癌细胞增殖和转移  

The regulation of proliferation and metastasis of colon cancer cells by inhibition of STAT3 activation with Salidroside

作　　者：葛朝伦[1] 赵斐 潘芳杰[3] 陈良[1] 徐晓琴 GE Chao-lun;ZHAO Fei;PAN Fang-jie;CHEN Liang;XU Xiao-qin(Department of Pharmacy,Traditional Chinese Medicine Hospital Affiliated to Xinjiang Medical University,Xinjiang Urumqi 830000,China;Health Care Department,Xinjiang Uygur Autonomous Region Maternal and Child Care Hospital,Xinjiang Urumqi 830001,China;Anorectal Department,Traditional Chinese Medicine Hospital Affiliated to Xinjiang Medical University,Xinjiang Urumqi 830000,China;Xinjiang Uygur Autonomous Region Institute of Traditional Chinese Medicine and Ethnic Medicine,Xinjiang Urumqi 830002,China)

机构地区：[1]新疆医科大学附属中医医院药学部,新疆乌鲁木齐830000 [2]新疆维吾尔自治区妇幼保健院保健部,新疆乌鲁木齐830001 [3]新疆医科大学附属中医医院肛肠科,新疆乌鲁木齐830000 [4]新疆维吾尔自治区中药民族药研究所,新疆乌鲁木齐830002

出　　处：《中国医院药学杂志》2020年第19期2046-2050,2054,共6页Chinese Journal of Hospital Pharmacy

摘　　要：目的:研究红景天苷对结肠癌细胞增殖和转移的抑制作用,并探讨其分子机制。方法:采用平板克隆和CCK-8法检测结肠癌HCT116细胞活力,Transwell观察细胞侵袭与迁移能力,蛋白质印迹法检测增殖蛋白[c-Myc,细胞周期蛋白D1(cyclinD1)]、侵袭转移相关蛋白[E-钙黏附蛋白(E-cadherin)和基质蛋白酶9(MMP-9)]及JAK2/STAT3信号通路蛋白[STAT3、磷酸化STAT3(p-STAT3)、JAK2和磷酸化JAK2(p-JAK2)]的表达。结果:平板克隆和CCK-8实验显示,与对照组相比,0.5,1,2μg·mL-1红景天苷显著抑制HCT116细胞的增殖,且在该范围内有浓度依赖性。Transwell实验显示,0.5,1,2μg·mL-1红景天苷分别作用于HCT116细胞24 h,细胞的侵袭、转移能力也逐渐降低(P<0.05)。蛋白质印迹法检测结果显示:与对照组相比,0.5,1,2μg·mL-1红景天苷组c-Myc、cyclinD1、MMP-9、p-STAT3、p-JAK2蛋白水平均明显降低(P<0.05),E-cadherin蛋白水平均升高(P<0.05),而JAK2、STAT3蛋白水平无明显差异(P>0.05)。与红景天苷组比较,红景天苷+Y705D组细胞增殖能力增强,迁移和侵袭细胞数增多(P<0.05),p-STAT3,c-Myc,cyclinD1,MMP-9蛋白表达增加,E-cadherin蛋白表达减少(P<0.05);而与Y705D组比较,红景天苷+Y705D组细胞增殖能力减弱(P<0.05),迁移和侵袭细胞数减少(P<0.05),p-STAT3、c-Myc、cyclinD1、MMP-9蛋白表达减少(P<0.05),E-cadherin蛋白表达增加(P<0.05)。结论:红景天苷抑制结肠癌细胞增殖和转移,其作用机制与抑制STAT3信号通路有关。OBJECTIVE To study the inhibitory effect of salidroside on proliferation and metastasis of colon cancer cells,and to explore its molecular mechanism.METHODS The viability of colon cancer HCT116 cells was detected by plate cloning and CCK-8 assay,the invasion and migration of HCT116 cells were observed by transwell,and the expression of proliferative proteins[c-Myc,cyclin D1],invasion and metastasis-related proteins[E-cadherin and matriptase 9(MMP-9)]and JAK2/STAT3 signaling pathway proteins[STAT3,phosphorylated STAT3(p-STAT3),JAK2 and phosphorylated JAK2(p-JAK2)]was detected by Western blotting.RESULTS Plate cloning and CCK-8 experiments showed that 0.5,1,2μg·mL-1 salidroside could significantly inhibited the proliferation of HCT116 cells in a concentration-dependent manner compared with the control group.Transwell experiments showed that after the treatment of 0.5,1,2μg·mL-1 salidroside for HCT116 cells for 24 h,and the invasion and metastasis ability of cells decreased gradually(P<0.05).Western blotting showed that the levels of c-Myc,cyclinD1,MMP-9,p-STAT3 and p-JAK2 in the 0.5,1,2μg·mL-1 salidroside group were significantly lower than those in the control group(P<0.05).The levels of-cadherin protein were significantly higher than those in the control group(P<0.05),while the levels of JAK2 and STAT3 proteins were not significantly different among the groups(P>0.05).Compared with the salidroside group,the salidroside+Y705 D group had enhanced cell proliferation,increased migration and invasion(P<0.05),p-STAT3,c-Myc,cyclinD1,MMP-9 protein expression Increased,E-cadherin protein expression decreased(P<0.05).Compared with the Y705 D group,the salidroside+Y705 D group had reduced cell proliferation capacity(P<0.05),and reduced the number of migrated and invasive cells(P<0.05).MMP-9 protein expression decreased(P<0.05),E-cadherin protein expression increased(P<0.05).CONCLUSION Salidroside inhibits the proliferation and metastasis of colon cancer cells,and its mechanism is related to the inhibition of STAT3 sig

关 键 词：红景天苷 转录激活因子 结肠癌 增殖 转移 

分 类 号：R96[医药卫生—药理学]