Rescued expression of WIF-1 in gallbladder cancer inhibits tumor growth and induces tumor cell apoptosis with altered expression of proteins.

Abstract

As a highly conserved metabolic pathway, the Wnt signaling pathway is involved in cell differentiation, proliferation and several other processes. In normal cells, this pathway is suppressed, and abnormal activation is often associated with tumor occurrence and development. In certain types of tumor, Wnt inhibitory factor 1 (WIF-1), an inhibitor of the Wnt pathway, inhibits tumor growth. However, the effect of the expression of WIF-1 on gallbladder cancer remains to be fully elucidated. In the current study, reverse transcription-quantitative polymerase chain reaction and western blotting were conducted. The present study demonstrated that, in gallbladder cancer, WIF-1 generally exhibited low levels of expression as a result of gene promoter methylation. Treatment with the drug, 5-aza-2-deoxycytidine, increased the expression of WIF-1 in the GBC-SD gallbladder cell line. In addition, a WIF-1-expression plasmid was transfected into GBC-SD cells, and it was found that cell proliferation, invasion and metastasis declined significantly, whereas the apoptotic rate increased. A nude mouse tumor transplantation experiment showed that the oncogenicity of the GBC-SD cells expressing WIF-1 was substantially lower, compared with that of the untransfected GBC-SD cells and of GBD-SD cells expressing the control plasmid. A fluorescent protein chip experiment showed that the restored expression of WIF-1 affected the expression of several cellular proteins. These alterations may explain the different biological behavior of the tumor cells expressing WIF-1. As an effective inhibitory factor of the Wnt signaling pathway, WIF-1 modulated the expression of proteins controlling the proliferation, apoptosis and metastasis of gallbladder tumor cells, thus suppressing the tumor. Therefore, WIF-1 may be an effective treatment target for gallbladder cancer.