MART-10, the new brand of 1α,25(OH)2D3 analog, is a potent anti-angiogenic agent in vivo and in vitro

被引：14

作者：

Chiang, Kun-Chun ^{[1
]}

Sun, Chi-Chin ^{[2
]}

Chen, Ming-Huang ^{[3
,4
]}

Huang, Chi-Ying ^{[5
,6
]}

Hsu, Jun-Te ^{[7
]}

Yeh, Ta-Sen ^{[7
]}

Chen, Li-Wei ^{[8
]}

Kuo, Sheng-Fong ^{[9
]}

Juang, Horng-Heng ^{[10
]}

Takano, Masashi ^{[11
]}

Kittaka, Atsushi ^{[11
]}

Chen, Tai C. ^{[12
]}

Yeh, Chun-Nan ^{[7
]}

Pang, Jong-Hwei S. ^{[13
]}

机构：

[1] Chang Gung Univ, Chang Gung Mem Hosp, Dept Gen Surg, Keelung, Taiwan

[2] Chang Gung Univ, Chang Gung Mem Hosp, Dept Ophthalmol, Keelung, Taiwan

[3] Taipei Vet Gen Hosp, Div Hematol & Oncol, Dept Med, Taipei, Taiwan

[4] Natl Yang Ming Univ, Fac Med, Taipei 112, Taiwan

[5] Natl Yang Ming Univ, Inst Clin Med, Inst Biopharmaceut Sci, Taipei 112, Taiwan

[6] Natl Yang Ming Univ, Genome Res Ctr, Taipei 112, Taiwan

[7] Chang Gung Univ, Dept Gen Surg, Chang Gung Mem Hosp, Taoyuan 333, Taiwan

[8] Chang Gung Univ, Chang Gung Mem Hosp, Dept Gastroenterol, Keelung, Taiwan

[9] Chang Gung Univ, Chang Gung Mem Hosp, Dept Endocrinol & Metab, Keelung, Taiwan

[10] Chang Gung Univ, Dept Anat, Coll Med, Kwei Shan Taoyuan 333, Taiwan

[11] Teikyo Univ, Fac Pharmaceut Sci, Sagamihara, Kanagawa 2525195, Japan

[12] Boston Univ, Sch Med, Boston, MA 02118 USA

[13] Chang Gung Univ, Grad Inst Clin Med Sci, Coll Med, Taoyuan 333, Taiwan

来源：

JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY | 2016年 / 155卷

关键词：

Angiogenesis; MART-10; Vitamin D; HUVEC; 1; alpha; 25(OH)(2)D-3; ENDOTHELIAL GROWTH-FACTOR; VITAMIN-D ANALOG; ENHANCED CHEMOTHERAPEUTIC POTENCY; 19-NOR-2-ALPHA-(3-HYDROXYPROPYL)-1-ALPHA; 25-DIHYDROXYVITAMIN D-3; TYROSINE KINASE; DOWN-REGULATION; CELL MIGRATION; UP-REGULATION; CANCER-CELLS; PROSTATE;

D O I：

10.1016/j.jsbmb.2015.09.022

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Background: Angiogenesis is the hall marker for cancer growth and metastasis. Thus, anti-angiogenesis emerges as a new way to treat cancer. 1 alpha,25(OH)(2)D-3 is recently getting popular due to the non-mineral functions, which have been applied fore cancer treatment. The newly-synthesized 1 alpha,25(OH)(2)D-3 analog, MART-10, has been proved to be much more potent than 1 alpha,25(OH)(2)D-3 regarding inhibiting cancer cells growth and metastasis without inducing hypercalcemia in vivo. In this study, we aimed to investigate the effect of MART-10 and 1 alpha,25(OH)(2)D-3 on angiogenesis in vitro and in vivo. Methods and results: MART-10 and 1 alpha,25(OH)(2)D-3 were able to repress VEGFA-induced human umbilical vein endothelial cells (HUVECs) migration, invasion and tube formation, but not proliferation, with MART-10 much more potent than 1 alpha,25(OH)(2)D-3. The Chick Chorioallantoic Membrane (CAM) assay and matrigeal angiogenesis assay further confirmed the in vivo more potent anti-angiogenesis effect of MART-10. MART-10 inhibited the VEGFA-induced HUVECs angiogenesis process through downregulation of Akt and Erk 1/2 phosphorylation. The VEGFA-VEGFR2 (VEGF receptor 2) axis is the main signal transducing pathway to stimulate angiogenesis. A positive autocrine manner was found for the first time in HUVECs as treated by VEGFA, which induced VEGFA expression and secretion, and VEGFR2 expression. MART-10 and1 alpha,25(OH)(2)D-3 were demonstrated to be able to repress this positive autocrine manner, thus inhibiting angiogenesis. Conclusions: MART-10 and 1 alpha,25(OH)(2)D-3 both are effective anti-angiogenesis agents. Given MART-10 is much more potent than 1 alpha,25(OH)(2)D-3 and active in vivo without obvious side effect, MART-10 should be deemed as a promising anti-cancer agent. (C) 2015 Elsevier Ltd. All rights reserved.

引用

页码：26 / 34

页数：9

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