UNASSIGNED: Normal Nthy-ori 3-1 thyroid cells and two PTC cell lines (BHP10-3 and TPC-1), which were used as RET fusion models of PTC, were used to study Klotho. Klotho expression was analyzed by Western blotting. Klotho overexpression cell lines were constructed using the two types of PTC cells. Cell proliferation and apoptosis were assessed. Western blotting was used to detect the expression of proteins in the Wnt/β-catenin pathway. In addition, an activator and an inhibitor of the Wnt/β-catenin pathway were used to confirm that Klotho regulates the pathway in PTC cells. Mice were used to analyze the in vivo effect of Klotho on tumor growth and the Wnt/β-catenin pathway.
UNASSIGNED: In BHP10-3 and TPC-1 cells, Klotho expression was low. After Klotho overexpression, the cell proliferation was significantly suppressed and apoptosis was significantly increased (p<0.05). Wnt1, β-catenin, and CyclinD1 expression were also significantly decreased after Klotho overexpression (p<0.05). Administration of the Wnt/β-catenin pathway activator attenuated the effect of Klotho overexpression (p<0.05). In vivo, the tumor growth was suppressed, and apoptosis of the cancer cells in the tumors were increased after Klotho overexpression. However, injection of the Wnt/β-catenin pathway activator attenuated the effects of Klotho overexpression.
UNASSIGNED: Klotho inhibits cell proliferation in RET fusion models of PTC by inhibiting the Wnt/β-catenin pathway, providing a potential target for developing treatment for PTC.
■正常Nthy-ori3-1甲状腺细胞和两个PTC细胞系(BHP10-3和TPC-1),它们被用作PTC的RET融合模型,被用来研究Klotho.通过Western印迹分析Klotho表达。使用两种类型的PTC细胞构建Klotho过表达细胞系。评估细胞增殖和凋亡。采用Western印迹法检测Wnt/β-catenin通路中蛋白质的表达。此外,使用Wnt/β-catenin途径的激活剂和抑制剂来证实Klotho调节PTC细胞中的途径。使用小鼠分析Klotho对肿瘤生长和Wnt/β-连环蛋白途径的体内作用。
■在BHP10-3和TPC-1单元格中,Klotho表达很低。Klotho过表达后,细胞增殖显著抑制,凋亡显著增加(p<0.05)。Wnt1,β-连环蛋白,在Klotho过表达后,CyclinD1的表达也显著降低(p<0.05)。Wnt/β-连环蛋白途径激活剂的施用减弱了Klotho过表达的作用(p<0.05)。在体内,肿瘤生长受到抑制,Klotho过表达后,肿瘤中癌细胞的凋亡增加。然而,注射Wnt/β-连环蛋白途径激活剂减弱了Klotho过表达的作用。
■Klotho通过抑制Wnt/β-catenin通路抑制PTC的RET融合模型中的细胞增殖,为开发PTC的治疗提供了潜在的目标。