cholecalciferol and Insulinoma

Pancreatic neuroendocrine tumors (PanNETs) are usually diagnosed in an advanced stage. Most patients with PanNETs die of metastasis. Vascular endothelial growth factor-A (VEGF-A) is a strong stimulator of angiogenesis and tumor metastasis. We aimed to investigate the effect of MART-10 [19-nor-2α-(3-hydroxypropyl)-1α,25(OH). Migration and invasion assays, western blot, and immunofluorescent staining were applied in this study.. VEGF-A increased PanNET cell migration and invasion, which was attenuated by 1α,25(OH). Our data indicate that MART-10 could be deemed a promising drug for PanNET treatment.

Topics: Animals; Apoptosis; Cell Movement; Cell Proliferation; Cholecalciferol; Gene Expression Regulation, Neoplastic; Insulinoma; Rats; Tumor Cells, Cultured; Vascular Endothelial Growth Factor A

Neuroendocrine tumors (NETs) are the second most common digestive malignancy. For advanced NETs, survival is not satisfactory. Vitamin D has emerged as a promising anticancer drug.. Cell proliferation assay, western blot, flow cytometry, and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assays were applied.. We demonstrated that RIN-m cells, neuroendocrine tumor cells, expressed vitamin D receptor (VDR) and VDR expression increased with increasing exposure to 1α,25-dihydroxyvitamin D3 [1α,25(OH)2D3] or MART-10, a 1α,25(OH)2D3 analog. MART-10 had anti-growth effect on RIN-m cells comparable to those of 1α,25(OH)2D3 The growth inhibition of both drugs was mediated by induction of cell-cycle arrest at G0/G1 phase and apoptosis. Western blot assay further revealed that this G0/G1 arrest was due to the up-regulation of p27 and down-regulation of cyclin dependent kinase 4 (CDK4), with MART-10 also reducing CDK6. Apoptosis induction was further supported by increased cleaved caspase-3 expression after treatment.. MART-10 appears to be a promising regimen for NET treatment.

Topics: Animals; Apoptosis; Calcitriol; Cell Growth Processes; Cell Line, Tumor; Cholecalciferol; Cyclin-Dependent Kinase 4; Cyclin-Dependent Kinase Inhibitor p27; G1 Phase Cell Cycle Checkpoints; Insulinoma; Neuroendocrine Tumors; Pancreatic Neoplasms; Rats; Receptors, Calcitriol