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. 2018 May;15(5):7403-7408.
doi: 10.3892/ol.2018.8220. Epub 2018 Mar 9.

Potential suppressive effects of theophylline on human rectal cancer SW480 cells in vitro by inhibiting YKL-40 expression

Hong Peng  1   2 , Qiang Su  3 , Zhong-Chao Lin  1 , Xiu-Hua Zhu  1 , Ming-Sha Peng  1 , Zhen-Bing Lv  4
Affiliations
Free PMC article

Potential suppressive effects of theophylline on human rectal cancer SW480 cells in vitro by inhibiting YKL-40 expression

Hong Peng et al. Oncol Lett. 2018 May.
Free PMC article

Abstract

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.

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Figures

Figure 1.
Figure 1.
Effect of theophylline on SW480 cell viability.
Figure 2.
Figure 2.
YKL-40 expression. (A) YKL-40 expression levels in different group. Lane 1, treatment group (10−4 mol/l theophylline); lane 2, negative (medium-treated) group; lane 3, blank (untreated) group. Bottom bands represents YKL-40; Top bands represents β-actin. (B) Densitometric analysis. YKL-40, Chitinase-3-like-1 protein.
Figure 3.
Figure 3.
Cell cycle analysis. (A) The negative (medium-treated) group; (B) The blank (untreated) group; (C) The treatment (10−4 mol/l theophylline) group.
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