Determining the effect of transforming growth factor-β1 on cdk4 and p27 in gastric cancer and cholangiocarcinoma

Oncol Lett. 2013 Feb;5(2):694-698. doi: 10.3892/ol.2012.1024. Epub 2012 Nov 13.

Abstract

Gastric cancer and cholangiocarcinoma are problematic throughout the world due to their destructive malignancy. In attempts to treat cholangiocarcinoma and gastric cancer, researchers often explore the effects of transforming growth factor-β1 (TGF-β1). TGF-β1 plays a crucial role in causing cell cycle arrest and fibrosis in cancer cells. The present study aimed to identify whether TGF-β1 is capable of functioning as an antitumor agent in two cancer cell lines; cholangiocarcinoma and gastric cancer. The downregulation of cyclin dependent kinase (cdk) 4 and the upregulation of p27 were investigated, in order to identify possible antitumor functions of TGF-β1. A number of different methods were implemented, including cell proliferation assay, bicinchoninic acid (BCA) assay and western blot analysis with TGF-β1, AGS (human gastric cancer cell line) and SUN-1196 (human cholangiocarcinoma cell line). In the AGS study, cdk4 values decreased from 1.000 to 0.670 and then to 0.664, with increasing TGF-β1 concentrations of 0, 0.5 and 5 ng/ml, respectively. By contrast, p27 values increased from 1.000 to 1.391 and then to 1.505, with increasing TGF-β1 concentrations of 0, 0.5 and 5 ng/ml, respectively. In the SUN-1196 study, p27 values increased from 0.548 to 0.807 and then to 0.844 with increasing TGF-β1 concentrations of 5, 25 and 50 ng/ml, respectively. Certain concentrations of TGF-β1 play antitumor roles in gastric cancer through the down-regulation of cdk4 and upregulation of p27. Certain TGF-β1 concentrations also have antitumor roles in cholangiocarcinoma through the upregulation of p27. With these results, we came a step closer to finding a cure for cholangiocarcinoma and gastric cancer.

Keywords: cholangiocarcinoma; cyclin dependent kinase 4; gastric cancer; p27; transforming growth factor-β1.