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

Daru. 2014 Jun 5;22(1):47. doi: 10.1186/2008-2231-22-47.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

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