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ABSTRACT: Aims
It has been shown that nerve growth factor-? (NGF-?) promoted the initiation and progression of many tumors, and we have previously demonstrated that the expression of NGF-? was associated with tumor stage, nerve infiltration and lymph node metastasis in human hilar cholangiocarcinoma. However, whether NGF-? promotes tumor progression in human cholangiocarcinoma requires further investigation. Therefore, we aimed to determine the effects of NGF-? on the progression of human cholangiocarcinoma.Methods
Human cholangiocarcinoma QBC939 stable cell lines with over-expressed or silenced NGF-? genes were generated with pEGFP-N1-NGF-? and pGPU6/GFP/Neo-NGF-?-shRNA recombinant plasmids. Cell proliferation assay, colony formation assay, cell cycle analysis, apoptosis assay and tumorigenicity assay were performed to evaluate the role of NGF-? in the progression of human cholangiocarcinoma. In addition, human lymphatic endothelial cells were co-cultured with QBC939 culture supernatants, and the cell proliferation and migration abilities of the lymphatic endothelial cells were evaluated.Results
Forced expression of NGF-? in QBC939 cell lines promoted proliferation, colony formation and tumorigenicity in these cells and inhibited the apoptosis. However, down-regulation of NGF-? inhibited proliferation, colony formation and tumorigenicity, and increased the apoptotic rate of QBC939 cells. In addition, the NGF-? gain-of-function induced a high expression of vascular endothelial growth factor C and enhanced the proliferation and migration of lymphatic endothelial cells, while NGF-? loss-of-function showed opposite effects.Conclusions
We concluded that NGF-? promoted tumor progression in human cholangiocarcinoma QBC939 cells. Our results provided a new concept to understand the role of NGF-? in cholangiocarcinoma progression, and might provide important information for the development of new targeted therapies in human cholangiocarcinoma.
SUBMITTER: Yue XJ
PROVIDER: S-EPMC3634741 | biostudies-literature | 2013
REPOSITORIES: biostudies-literature
Yue Xiu-Jing XJ Xu Lei-Bo LB Zhu Man-Sheng MS Zhang Rui R Liu Chao C
PloS one 20130424 4
<h4>Aims</h4>It has been shown that nerve growth factor-β (NGF-β) promoted the initiation and progression of many tumors, and we have previously demonstrated that the expression of NGF-β was associated with tumor stage, nerve infiltration and lymph node metastasis in human hilar cholangiocarcinoma. However, whether NGF-β promotes tumor progression in human cholangiocarcinoma requires further investigation. Therefore, we aimed to determine the effects of NGF-β on the progression of human cholangi ...[more]