评估 TGF-β 受体 I 抑制剂（SD-208）对人结肠腺癌的抗肿瘤活性。

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

机构信息

Stem Cells Preparation Uinte, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran.

出版信息

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

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.

背景

转化生长因子-β（TGF-β）途径参与了原发性肿瘤的进展，并在相当一部分人类癌症（如结直肠癌（CRC））中促进转移。因此，通过抑制剂阻断 TGF-β途径信号可能是 CRC 治疗的一种有价值的工具。

方法

为了评估系统靶向 TGF-β途径对 CRC 治疗效果的疗效，我们研究了 TGβRI（TGF-β 受体 1）或 TβRI 激酶抑制剂 SD-208 对 SW-48、结肠腺癌细胞的影响。在这项工作中，通过甲基噻唑基四唑（MTT）和溴脱氧尿苷（BrdU）测定法研究了体外细胞增殖。此外，通过苏木精和伊红以及 Ki-67 和 CD34 标志物染色分别进行了组织病理学和免疫组织化学评估。