PT  - JOURNAL ARTICLE
AU  - CHIANG, KUN-CHUN
AU  - YEH, CHUN-NAN
AU  - PANG, JONG-HWEI S.
AU  - HSU, JUN-TE
AU  - YEH, TA-SEN
AU  - CHEN, LI-WEI
AU  - KUO, SHENG-FONG
AU  - HSIEH, PO-JEN
AU  - PAN, YI-CHUN
AU  - TAKANO, MASASHI
AU  - CHEN, TAI C.
AU  - FENG, TSUI-HSIA
AU  - KITTAKA, ATSUSHI
AU  - JUANG, HORNG-HENG
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.