Abstract: Background and purpose: Chemotherapy is an important treatment for colon cancer, which often consists of platinum drugs. However, chemotherapy resistance can affect efficacy of drug and prognosis of patient with colon cancer, and its mechanism is related to abnormal gene expression. Golgi phosphoprotein 3 (GOLPH3) is a new oncogene, which is overexpressed in colon cancer tissue. It can promote the proliferation of colon cancer cells, and is associated with poor prognosis. At present, the relationship between the GOLPH3 gene overexpression and the resistance to platinum drugs in colon cancer is still unknown. This study aimed to investigate the effect of GOLPH3 gene silencing on reversing cisplatin resistance and its mechanism in human colon cell HT29. Methods: Colon cancer cells were divided into five groups. ① Control group: HT29 human colon cancer cells; ② Transfection group: GOLPH3 gene silencing of HT29 cells by siRNA; ③ Experimental group 1: HT29 cells treated with cisplatin; ④ Experimental group 2: HT29 siRNA-GOLPH3 transfected cells treated with cisplatin; ⑤ Experimental group 3: HT29 cells treated with cisplatin and extracellular regulated protein kinases (ERK1/2) inhibitor PD98059. The proliferation and colony formation capability of HT29 cell were measured respectively by methyl thiazolyl tetrazolium (MTT) and plate colony formation assays. The expressions of GOLPH3、P-gp、ERK1/2 and pERK1/2 in HT29 cell were detected by Western blot. Results: Absorbance (D) at 490 nm in experimental group 1 and experimental group 2 was significantly lower than that in the control group (P<0.05), while the D₄₉₀ value in experimental group 2 was significantly decreased compared with experimental group 1 (P<0.01). The numbers of colony count in experimental group 1 and experimental group 2 were significantly lower than that in the control group (P<0.01), while the number of colony count in experimental group 2 was significantly decreased compared with experimental group 1 (P<0.001). Compared with experimental group 1, the expressions of GOLPH3, P-gp and pERK1/2 proteins in experimental group 2 were significantly decreased (P<0.01). The expression of P-gp protein in experimental group 3 was significantly lower than that in experimental group 1 (P<0.01). Conclusion: Silencing of GOLPH3 gene could reverse the resistance of human colon cancer HT29 cells to cisplatin by deactivating mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling pathway.

Key words: Golgi phosphoprotein 3, Colon cancer cells, Mitogen-activated protein kinase/extracellular signal-regulated kinase signaling pathway, Chemoresistance, Cisplatin