Lu X F, Xia X F, Chen G
Department of Gastrointestinal Surgery, Nanjing Drum Tower Hospital, Nanjing 210008, China.
Zhonghua Zhong Liu Za Zhi. 2016 Jul;38(7):499-503. doi: 10.3760/cma.j.issn.0253-3766.2016.07.004.
To investigate the role of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) in the metastasis of colorectal cancer and underlying mechanisms.
A colorectal cancer LoVo cell line transfected with a lentivirus vector stably expressinga shRNA targeting PGC-1αwas established. Cell proliferation was detected by CCK8 array. Migration and invasion were determined by Transwell assay. The expressions of epithelial-mesenchymal transition (EMT) markers were examined by western blot analysis.
Down-regulation of PGC-1α significantly inhibited the migration (74.4±4.5 versus 31.4±3.8,P<0.05), invasion (55.0±7.7 versus 17.6±5.0,P<0.05) and anoikis resistance (32.3±4.3)% versus (54.3±4.8)%,P<0.05, of LoVo cells. However, knockdown of PGC-1α had little effect on cell proliferation. Moreover, knockdown of PGC-1α induced EMT of LoVo cells by up-regulating E-cadherin and down-regulating vimentin. Alternatively, the expression of PGC-1α was induced by cell detachment. PGC-1αexpression was also higher in the colorectal cancer tissues than that in para-cancerous tissues, and its expression in the invading front area was higher than that in the tumor center area.
PGC-1α plays an important role in the metastasis of colorectal cancer, which may promote the invasion and anoikis resistance of colorectal cancer cells through EMT induction.
探讨过氧化物酶体增殖物激活受体γ共激活因子1α（PGC-1α）在结直肠癌转移中的作用及潜在机制。
构建稳定表达靶向PGC-1α的短发夹RNA（shRNA）的慢病毒载体，转染结直肠癌LoVo细胞系。采用CCK8法检测细胞增殖。通过Transwell实验检测细胞迁移和侵袭能力。采用蛋白质免疫印迹法检测上皮-间质转化（EMT）标志物的表达。
下调PGC-1α可显著抑制LoVo细胞的迁移（74.4±4.5对31.4±3.8，P<0.05）、侵袭（55.0±7.7对17.6±5.0，P<0.05）及失巢凋亡抵抗能力（32.3±4.3)%对(54.3±4.8)%，P<0.05）。然而，敲低PGC-1α对细胞增殖影响较小。此外，敲低PGC-1α可通过上调E-钙黏蛋白和下调波形蛋白诱导LoVo细胞发生EMT。另外，细胞脱离可诱导PGC-1α表达。PGC-1α在结直肠癌组织中的表达高于癌旁组织，且在肿瘤侵袭前沿区域的表达高于肿瘤中心区域。
PGC-1α在结直肠癌转移中起重要作用，可能通过诱导EMT促进结直肠癌细胞的侵袭和失巢凋亡抵抗。
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