Guanylate‐binding protein‐2 inhibits colorectal cancer cell growth and increases the sensitivity to paclitaxel of paclitaxel‐resistant colorectal cancer cells by interfering Wnt signaling

Abstract Among the GTPase family members, guanylate‐binding protein‐1 (GBP‐1) is the most thoroughly studied member in a plethora of human cancers. GBP‐2, on the other hand, remains limitedly studied. We wonder how GBP‐2 participates in colorectal carcinoma (CRC) as well as the paclitaxel (PTX)‐resistance of CRC. In this study, the authors are determined to dig into the role that GBP‐2 plays in the sensitivity of CRC to PTX, therefore, possibly indicating a promising gene therapy target for CRC. Forced expression of GBP‐2 gene was done by plasmid transfection. Reverse transcriptase‐polymerase chain reaction and immunoblot were conducted to detect the expression of GBP‐2 messenger RNA (mRNA) and protein, respectively. Colony foci formation assay, transwell invasion assay, and flow cytofluorometry were done to determine the proliferation, invasion, and apoptosis of PTX‐resistant and PTX‐sensitive CRC cell lines, respectively. The level of GBP‐2 mRNA and protein in PTX‐resistant CRC cell lines was significantly lower than in nonresistant cell lines. Forced exogenous expression of GBP‐2 in PTX‐resistant CRC cell lines resulted in more sensitivity to PTX because of the demonstration of less cell proliferation, invasion, and more apoptosis. Wnt signaling was suppressed when GBP‐2 was upregulated by transfection of GBP‐2 overexpression plasmids, and Wnt signaling did not affect GBP‐2 expression. GBP‐2 upregulation could enhance the killing effect of PTX in both PTX‐sensitive CRC cells and PTX‐resistant CRC cells by suppressing Wnt signaling.