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

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.

• Authors: Abolfazl Akbari, Saeid Amanpour, Samad Muhammadnejad, Mohammad Hossein Ghahremani, Seyed Hamidollah Ghaffari, Ahmad Reza Dehpour, Gholam Reza Mobini, Fatemeh Shidfar, Mahdi Abastabar, Ahad Khoshzaban, Ebrahim Faghihloo, Abbas Karimi, Mansour Heidari
• Journal: Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences (Daru) Vol. 22 Pg. 47 (Jun 05 2014) ISSN: 2008-2231 [Electronic] Switzerland
• PMID: 24902843 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Pteridines
• SD-208
• Transforming Growth Factor beta

Topics

• Adenocarcinoma (drug therapy, pathology)
• Animals
• Antineoplastic Agents (pharmacology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Colonic Neoplasms (drug therapy, pathology)
• Female
• Humans
• Mice
• Mice, Inbred C57BL
• Neovascularization, Pathologic (metabolism)
• Pteridines (pharmacology)
• Transforming Growth Factor beta (antagonists & inhibitors, metabolism)
• Xenograft Model Antitumor Assays