MART-10, the vitamin D analog, is a potent drug to inhibit anaplastic thyroid cancer cell metastatic potential

作者：Chiang Kun Chun; Kuo Sheng Fong; Chen Chih Hung; Ng Sohching; Lin Shu Fu; Yeh Chun Nan; Chen Li Wei; Takano Masashi; Chen Tai C; Juang Horng Heng; Kittaka Atsushi^*; Lin Jen Der; Pang Jong Hwei S

来源：Cancer Letters, 2015, 369(1): 76-85.

DOI：10.1016/j.canlet.2015.07.024

• Anaplastic thyroid cancer
• Vitamin D
• MART-10
• Migration
• Invasion
• EMT

The survival rate of anaplastic thyroid cancer (ATC) is still very poor due to its fast growth and high metastatic potential; Currently, no effective treatment is available. The active form of vitamin D3, 1 alpha,25(OH)(2)D-3, has been shown to have a anti-metastatic effect in pre-clinical studies, however induction of hypercalcemia hampered its clinical application. The new class of less-calcemic vitamin D analog, 19-nor-2 alpha-(3-hydroxypropyl)-1 alpha,25-dihydroxyvitamin D-3 (MART-10), is much more potent than 1 alpha,25(OH)(2)D-3 to repress cancer growth and metastasis in a variety of cancers. In this study, we demonstrated that both 1 alpha,25(OH)(2)D-3 and MART-10 could effectively inhibit the migration and invasion of ATC cells, 8305C and 8505C, with MART-10 much more potent than 1 alpha,25(OH)(2)D-3. The anti-metastatic effect of 1 alpha,25(OH)(2)D-3 and MART-10 on ATC cells is mediated by reversal of cadherin switch (upregulation of E-cadherin and downregulation of N-cadherin), which led to the attenuation of EMT process, and decrease of F-actin formation. We further showed that the expressions of Slug, the EMT-related transcriptional factor, and MMP-9 were inhibited by 1 alpha,25(OH)(2)D-3 and MART-10 in 8505C cells, but not in 8303C cells. Since metastasis is the important cause of ATC-related death, our results strongly encourage the further in vivo study of MART-10 application against ATC.

• 出版日期2015-12-1
• 单位长春大学