【摘要】 观察糖原合酶激酶-3β(GSK-3β)在牛磺酸(Tau)抑制结直肠癌(CRC)侵袭转移中的作用,探讨Tau抑制结直肠癌侵袭转移分子机制。选用人结直肠癌SW480和HT29细胞为研究对象,用浓度为40～200 mmoL Tau处理细胞;Transwell小室和细胞划痕愈合实验检测细胞侵袭、迁移能力,Western blot检测细胞EMT标志性蛋白(E-cadherin, N-cadherin, Vimentin),基质金属蛋白酶2/7(MMP2/7)和AKT/GSK-3β通路相关蛋白水平。与正常对照组比较,Tau可浓度依赖性抑制CRC细胞侵袭和迁移,上调CRC上皮标志物E-cadherin表达,下调EMT间质标志物N-cadherin, Vimentin和MMPs表达;降低AKT和p-AKT水平,提高PTEN,GSK-3β及p-GSK-3β表达水平(P<0.05)。与p-EGFP-GSK-3β或Tau组比较,p-EGFP-GSK-3β+Tau组细胞迁移和侵袭数量有显著性降低(P<0.01);与Tau组或p-EGFP-GSK-3β组比较,p-EGFP-GSK-3β+Tau组E-Cadherin、GSK-3β蛋白表达有显著升高(P<0.01),而N-Cadherin, Vimentin,β-Catenin, MMP2/7和AKT蛋白表达均有显著降低(P<0.01)。牛磺酸可通过调控AKT/GSK-3β通路抑制结直肠癌细胞侵袭转移。更多还原

【Abstract】 The effect of taurine(Tau) on the inhibition of invasion and metastasis of colorectal cancer(CRC) was observed and the molecular mechanism of Tau inhibiting invasion and metastasis of CRC was explored.Human colorectal cancer SW480 and HT29 cells were selected as the research objects, and the cells were treated with Tau at a concentration of 40-200 mmoL.Transwell chamber and cell scar healing assay were used to detect cell invasion and migration ability.Western blot was used to detect EMT signature proteins E-cadherin N-cadherin, Vimentin, matrix metalloproteinase 2/7(MMP2/7) and AKT/GSK-3β pathway related proteins.Compared with normal control group, Tau inhibited the invasion and migration of CRC in a concentration-dependent manner, up-regulated the expression of CRC epithelial marker E-cadherin, and down-regulated the expression of EMT interstitial marker N-cadherin, Vimentin and MMPs.AKT and p-AKT levels were decreased, and PTEN,GSK-3β and p-GSK-3β expression levels were increased(P<0.05).Compared with p-EGFP-GSK-3β or Tau group, the number of cell migration and invasion in p-EGFP-GSK-3β +Tau group was significantly decreased(P<0.01);Compared with Tau group or p-EGFP-GSK-3β group, the expression of E-cadherin GSK-3β protein in p-EGFP-GSK-3β+Tau group was significantly increased(P<0.01),and the expression of N-cadherin, Vimentin, β-catenin MMP2,MMP7 and AKT was significantly decreased(P<0.01).Taurine can inhibit the invasion and metastasis of colorectal cancer cells by regulating the Akt/GSK-3β pathway.更多还原