EFFECT OF FIBULIN-2 ON PROLIFERATION AND APOPTOSIS OF GASTRIC CANCER CELLS BY INHIBITING TGF-β1/SMAD4 SIGNAL PATHWAY

GUANGYAO WANG, LIMING TANG, JUN QIAN, HAOJUN YANG

Department of Gastrointestinal Surgery, The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University, Changzhou City, China

Objective: To investigate the effect of fibulin-2 on the proliferation and apoptosis of gastric cancer cells and its mechanism.

Methods: This study analysed the expression of fibulin-2 and TGF-β1 in 36 gastric cancer samples and 36 normal gastric epithe- lial samples with immunohistochemistry and RT-PCR, respectively. The expression of fibulin-2 and pathological features of these clinical cases were also studied. In addition, the expression levels of fibulin-2, TGF-β1, Smad4 and pSmad4 in various gastric cancer cell lines were determined using RT-PCR and Western blot. Through transfecting a fibulin-2 mimic, we observed TGF-β1 expression at different times. In order to validate that fibulin-2 impacts the proliferation and apoptosis of gastric cancer cells through the TGF-β1/Smad4 signal pathway, we used MTT and flow cytometry to analyse the proliferation and apoptosis of cells in different groups, successively.

Results: The expression of fibulin-2 was much lower in the gastric cancer samples than in the control group, but the expression of TGF-β1 was much higher in the gastric cancer samples. The expression and differentiation degree of fibulin-2 were significantly related to TNM staging. Thereinto, the expression of fibulin was positively associated with differentiation degree, and the positive rate of fibulin- 2 declined from stage I to stage IV, successively. Besides, the fibulin-2 mimic greatly restrained the proliferation of gastric cancer cells and promoted their apoptosis compared to the control group.

Conclusions: Fibulin-2 promotes the apoptosis of gastric cancer cells and restrains their proliferation through inhibiting the TGF-β1/Smad4 signal pathway.