PT - JOURNAL ARTICLE AU - KUN-CHUN CHIANG AU - CHUN-NAN YEH AU - JONG-HWEI S. PANG AU - JUN-TE HSU AU - TA-SEN YEH AU - LI-WEI CHEN AU - SHENG-FONG KUO AU - PO-JEN HSIEH AU - YI-CHUN PAN AU - MASASHI TAKANO AU - TAI C. CHEN AU - TSUI-HSIA FENG AU - ATSUSHI KITTAKA AU - HORNG-HENG JUANG TI - 1α,25(OH)<sub>2</sub>D<sub>3</sub> Analog, MART-10, Inhibits Neuroendocrine Tumor Cell Growth Through Induction of G<sub>0</sub>/G<sub>1</sub> Cell-cycle Arrest and Apoptosis DP - 2016 Jul 01 TA - Anticancer Research PG - 3307--3313 VI - 36 IP - 7 4099 - http://ar.iiarjournals.org/content/36/7/3307.short 4100 - http://ar.iiarjournals.org/content/36/7/3307.full SO - Anticancer Res2016 Jul 01; 36 AB - Background: 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. Materials and Methods: Cell proliferation assay, western blot, flow cytometry, and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assays were applied. Results: 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. Conclusion: MART-10 appears to be a promising regimen for NET treatment.