The combination of tetraiodothyroacetic acid and cetuximab inhibits cell proliferation in colorectal cancers with different K-ras status

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• 作者：Yee-Shin Lee^a ; Yu-Tang Chin^b ; Yu-Chen S.H. Yang^c ; Po-Li Wei^d ; Han-Chung Wu^e ; Ai Shih^f ; Yueh-Tong Lu^b ; Jens Z. Pedersen^g ; Sandra Incerpi^h ; Leroy F. Liu^b ; Hung-Yun Lin^a ; ^b ; ^{linhy@tmu.edu.tw" class="auth_mail" title="E-mail the corresponding author} ; Paul J. Davisⁱ ; ^j
• 关键词：Colorectal cancer ; Thyroid hormone ; Tetrac ; NDAT ; Cetuximab
• 刊名：Steroids
• 出版年：2016
• 出版时间：July 2016
• 年：2016
• 卷：111
• 期：Complete
• 页码：63-70
• 全文大小：734 K

文摘

Thyroid hormone induces cancer cell proliferation through its cell surface receptor integrin αvβ3. Acting via integrin αvβ3, the deaminated T₄ analog tetraiodothyroacetic acid (tetrac), and its nanoparticle formulation nano-diamino-tetrac (NDAT) could inhibit cell proliferation and xenograft growth. In this study, we investigated the T₄ effects on proliferation in colorectal cancer cell lines based on the proliferation marker expressions at both mRNA and protein levels. The effects of tetrac/NDAT, the monoclonal anti-EGFR antibody cetuximab, and their combinations on colorectal cancer cell proliferation were examined according to the relevant gene expression profiles and cell count analysis. The results showed that T₄ significantly enhanced PCNA, Cyclin D1 and c-Myc levels in both K-ras wild type HT-29 and mutant HCT 116 cells. In HCT 116 cells, the combination of NDAT and cetuximab significantly suppressed the mRNA expressions of proliferative genes PCNA, Cyclin D1, c-Myc and RRM2 raised by T₄ compared to cetuximab alone. In addition, T₄-suppressed mRNA expressions of pro-apoptotic genes p53 and RRM2B could be significantly elevated by the combination of NDAT and cetuximab compared to cetuximab alone. In the K-ras mutant HCT 116 cells, but not in the K-ras wild type COLO 205 cells, the combinations of tetrac/NDAT and cetuximab significantly reduced cell proliferation compared to cetuximab alone. In conclusion, T₄ promoted colorectal cancer cell proliferation which could be repressed by tetrac and NDAT. The combinations of tetrac/NDAT and cetuximab potentiated cetuximab actions in K-ras mutant colorectal cancer cells.