Department of Biochemistry, Dong-A University College of Medicine, Busan, Republic of Korea.
Department of Biochemistry, Dong-A University College of Medicine, Busan, Republic of Korea
Anticancer Res. 2020 Feb;40(2):653-664. doi: 10.21873/anticanres.13995.
BACKGROUND/AIM: Peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) is a master regulator of mitochondrial biogenesis and metabolism. We investigated the effect of PGC-1α knockdown in the human colorectal cancer cell line SW620, which highly expresses PGC-1α.
We established the PGC-1α shRNA-silenced SW620 stable cell line (PGC-1α shRNA-SW620 cells) and examined cell proliferation by cell counts and carboxyfluorescein succinimidyl ester (CFSE) staining, migration by wound-healing and transwell migration assay, and invasion by transwell assays.
PGC-1α knockdown inhibited cell proliferation, migration, and invasion in SW620 cells. Western blot analysis showed that p-AKT, p-GSK-3β, β-catenin, N-cadherin and vimentin expression were all reduced, but E-cadherin had increased expression in PGC-1α shRNA-SW620 cells. We also examined cell proliferation, migration, invasion and the expression of p-AKT, p-GSK-3β, β-catenin, N-cadherin, vimentin, and E-cadherin in PGC-1α overexpressing SW480 cells (a low PGC-1α expressing line). We observed a complete reversal of the results seen in the knockdown.
PGC-1α might regulate cell proliferation and invasion via AKT/GSK-3β/β-catenin pathway in SW620 and SW480 cells.
背景/目的：过氧化物酶体增殖物激活受体 γ 共激活因子 1α（PGC-1α）是线粒体生物发生和代谢的主要调节因子。我们研究了在高度表达 PGC-1α 的人结肠直肠癌细胞系 SW620 中敲低 PGC-1α 的效果。
我们建立了 PGC-1α shRNA 沉默的 SW620 稳定细胞系（PGC-1α shRNA-SW620 细胞），并通过细胞计数和羧基荧光素琥珀酰亚胺酯（CFSE）染色检测细胞增殖，通过划痕愈合和 Transwell 迁移实验检测迁移，通过 Transwell 实验检测侵袭。
PGC-1α 敲低抑制了 SW620 细胞的增殖、迁移和侵袭。Western blot 分析显示，p-AKT、p-GSK-3β、β-catenin、N-cadherin 和 vimentin 的表达均降低，而 E-cadherin 的表达在 PGC-1α shRNA-SW620 细胞中增加。我们还检测了 PGC-1α 过表达的 SW480 细胞（低 PGC-1α 表达系）中的细胞增殖、迁移、侵袭以及 p-AKT、p-GSK-3β、β-catenin、N-cadherin、vimentin 和 E-cadherin 的表达。我们观察到在敲低中观察到的结果完全逆转。
PGC-1α 可能通过 AKT/GSK-3β/β-catenin 通路调节 SW620 和 SW480 细胞的增殖和侵袭。
