GOLPH3 expression promotes the resistance of HT29 cells to 5‑fluorouracil by activating multiple signaling pathways.

The novel proto‑oncogene Golgi phosphoprotein (GOLPH)3 is overexpressed in a variety of tumor tissues and is associated with poor prognosis. The authors previously demonstrated that GOLPH3 gene is overexpressed in colorectal cancer tissues and promotes the proliferation of colonic cancer cells by activating the phosphatidylinositol‑3‑kinase/protein kinase B/the mammalian target of rapamycin and Wnt/β‑catenin signaling pathways. However, to the best of the authors' knowledge, if and how the GOLPH3 gene is involved in inducing resistance to colonic cancer chemotherapy has not been reported. In the present study, the association between the overexpression of the GOLPH3 gene and resistance of HT29 colonic cancer cells to 5‑fluorouracil (5‑FU) was investigated. Following confirmation of the effective silencing of the GOLPH3 gene, proliferation and apoptosis of colonic cancer cells were detected by MTT assay, colony formation assay and flow cytometry, and then the mechanism of GOLPH3‑induced resistance to 5‑FU chemotherapy in colonic cancer cells was investigated by western blotting. The results demonstrated that the expression of phosphorylated (p)‑glycoprotein and GOLPH3 was increased in HT29 cells following treatment with 5‑FU, which resulted in the development of drug resistance. Silencing GOLPH3 increased the sensitivity of HT29 cells to 5‑FU, reduced their tumorigenicity and partly reversed their resistance to 5‑FU. The expression of p‑extracellular signal‑regulated kinase (pERK)1/2 and β‑catenin was decreased, which indicated that its mechanism was associated with the activation of the mitogen‑activated protein kinase/ERK and Wnt/β‑catenin signaling pathways. Therefore, GOLPH3 may be a potential, novel target for reversing chemotherapy resistance in colon cancer.