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BackgroundCholangiocarcinoma (CCA) is a form of cancer that easily aggress to contiguous structures. Vascular endothelial growth factor (VEGF) and VEGF receptor 2 (VEGFR2) are increased in majority species of cancers and suppress tumor progression by blocking VEGF/VEGFR2. Apatinib is a highly selective VEGFR2 antagonist which has inhibitive effect on antiapoptotic and cell growth in CCA. While, the effect of apatinib cell migration and invasion in CCA is still unknown.MethodsCCA cell lines QBC939 and TFK-1 were transfected with siKDR to establish the KDR function loss cell model, and recombined human VEGF (rhVEGF) protein was added into the culture medium to enhance the VEGF expression. RT-qPCR and western bloting were used to detect the mRNA and protein expression levels of VEGFR2 to investigate whether it was effectively repressed or activated with rhVEGF or apatinib treatment. Then, MTT, wound healing assay, and transwell matrix assay were applied to measure the effect of apatinib and rhVEGF on cell viability, migration and invasion, respectively.ResultsThe mRNA and protein expressions of VEGFR2 were significantly reduced with KDR RNAi in both QBC939 and TFK-1 cells, and rhVEGF treatment increased these expression levels (p < 0.05). Apatinib dramatically suppressed VEGF-mediated cell migration and invasion at the concentration of 100 nM treatment and significantly decreased the expression of metastasis-associated protein such as Slug, snail and MMP9. Moreover, all of these inhibiting effects of apatinib depended on the VEGFR2 existence. In addition, VEGFR2/RAF/MEK/ERK and PI3K/AKT signal pathways were enhanced by the introduction of rhVEGF, but were dramatically suppressed after the apatinib treatment.ConclusionApatinib inhibit VEGF-mediated cell migration and invasion in CCA cell lines via inhibiting the VEGFR2/RAF/MEK/ERK and PI3K/AKT pathways. It will be a potentially effective targeted drug for CCA.

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Background:Esophageal cancer (EC) is a common cancer with high mortality because of its rapid progression and poor prognosis. Radiotherapy is one of the most effective treatments for EC. Three-dimensional conformal radiotherapy (3D-CRT) and intensity-modulated radiotherapy (IMRT) are 2 recently developed radiotherapy techniques. IMRT is believed to be more effective than 3D-CRT in target coverage, dose homogeneity, and reducing toxicity to normal organs. However, these advantages have not been demonstrated in the treatment of EC. This meta-analysis was performed to compare IMRT and 3D-CRT in the treatment of EC in terms of dose–volume histograms and outcomes including survival and toxicity.Methods:A literature search was performed in PubMed, Embase, and the Cochrane library databases from their inceptions to Dec 30, 2016. Two authors independently assessed the included studies and extracted data. The average percent irradiated volumes of adjacent noncancerous organs were calculated and compared between IMRT and 3D-CRT. The odds ratio of overall survival (OS), and radiation pneumonitis and radiation esophagitis was also evaluated.Results:Totally 7 studies were included. Of them, 5 studies (80 patients) were included in the dosimetric comparison, 3 studies (871 patients) were included in the OS analysis, and 2 studies (205 patients) were included in the irradiation toxicity analysis. For lung in patients receiving doses ≥20 Gy and heart in patients receiving dose = 50 Gy, the average irradiated volumes of IMRT were less than those from 3D-CRT. IMRT resulted in a higher OS than 3D-CRT. However, no significant difference was observed in the incidence of radiation pneumonitis and radiation esophagitis between 2 radiotherapy techniques.Conclusion:Our data suggest that IMRT-delivered high radiation dose produces significantly less average percent volumes of irradiated lung and heart than 3D-CRT. IMRT is superior to 3D-CRT in the OS of EC while shows no benefit on radiation toxicity.