Chitinase-3-like-1 protein (YKL-40), a member of the mammalian chitinase-like glycoproteins, serves a key role in the pathogenesis of rectal cancer. The present study examined the antitumor effect of theophylline, a pan-chitinase inhibitor, in rectal cancer in vitro and investigated the mechanism by which it acted. SW480 cell lines were treated with varying theophylline concentrations (10-2, 10-3, 10-4 and 10-5 mol/l). An MTT assay was used to observe cell proliferation and identify the optimal theophylline concentration. Western blotting was used to analyze YKL-40 expression. The cell cycle distribution of SW480 cell lines treated with theophylline was measured by flow cytometry. The angiopoietin-2 expression level was measured by ELISA. The expression levels of YKL-40 were evidently decreased in theophylline-treated SW480 cell lines. The proliferation of SW480 cells was inhibited following theophylline treatment, which was associated with G1 phase cell cycle arrest and a decrease in the expression of angiopoietin-2. The mechanism of theophylline action may involve the downregulation of YKL-40 expression, arrest of the cell cycle at G1 phase and inhibition of angiopoietin-2 expression. These results provide a rationale for the potential use of anti-YKL-40 and anti-angiogenic strategies in treating rectal cancer.
Keywords: angiopoietin-2; chitinase inhibitor; chitinase-3-like-1 protein; rectal cancer.