Evaluation of antitumor activity of a TGF-beta receptor I inhibitor (SD-208) on human colon adenocarcinoma.

Akbari, Abolfazl. and Amanpour, Saeid. and Muhammadnejad, Samad. and Ghahremani, Mohammad Hossein. and Ghaffari, Seyed Hamidollah. and Dehpour, Ahmad Reza. and Mobini, Gholam Reza. and Shidfar, Fatemeh. and Abastabar, Mahdi. and Khoshzaban, Ahad. and Faghihloo, Ebrahim. and Karimi, Abbas. and Heidari, Mansour. (2014) Evaluation of antitumor activity of a TGF-beta receptor I inhibitor (SD-208) on human colon adenocarcinoma. DARU Journal of Pharmaceutical Sciences, 22 (1).

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Abstract

BACKGROUND: Transforming growth factor-β (TGF-β) pathway is involved in primary tumor progression and in promoting metastasis in a considerable proportion of human cancers such as colorectal cancer (CRC). Therefore, blockage of TGF-β pathway signaling via an inhibitor could be a valuable tool in CRC treatment. METHODS: To evaluate the efficacy of systemic targeting of the TGF-β pathway for therapeutic effects on CRC, we investigated the effects of a TGβRI (TGF-β receptor 1) or TβRI kinase inhibitor, SD-208, on SW-48, colon adenocarcinoma cells. In this work, in vitro cell proliferation was studied by methyl thiazolyl tetrazolium (MTT) and bromo-2'-deoxyuridine (BrdU) assays. Also, the histopathological and immunohistochemical evaluations were conducted by hematoxylin and eosin, and Ki-67 and CD34 markers were stained, respectively. RESULTS: Our results showed no significant reduction in cell proliferation and vessel formation (170 ± 70 and 165 ± 70, P > 0.05) in treated SW-48 cells with SD-208 compared to controls. CONCLUSION: Our data suggested that SD-208 could not significantly reduce tumor growth and angiogenesis in human colorectal cancer model at least using SW-48 cells.

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