The Effects Of Cetuximab On The Overexpression Of Rho-GDI2 In The Colon Cancer Cells

Objective:The therapeutic options available for the treatment of metastatic CRC have significantly increased over the past years. Together with the advances in surgical techniques, the introduction of irinotecan and oxaliplatin first and drugs targeting VEGF or epidermal growth factor receptor(EGFR) later. Postoperative chemotherapy can improve patients’ life quality, prolong survival and reduce the recurrence rate. As for the patients who lose the chance of surgery therapeutic, maybe benefit from chemotherapy. With the high incidence of the primary or secondary resistance reduces the chemotherapy efficiency, therefore, the study of drug resistance in chemotherapy is imminent. Rho-specific guanine nucleotide dissociation inhibitor 2(Rho GDI2) has been found to be vital for carcinogenesis in bladder, breast, ovarian, pancreatic and gastric cancers, especially in regulating tumor cell apoptosis, invasion and metastasis, and angiogenesis effect, multidrug resistance,however only limited analyses have been done in the colorectal cancer. In this research we aimed to investigate the effect of cetuximab on the metastatic ability of HCT116-OE,which stable transfected Rho GDI2 using virus specifically expressed Rho GDI2、HCT116-VC(vector control) and HCT116-NC(normal control) cells. preliminarily study Rho GDI2-overexpression colorectal cancer cell may be related to resistance mechanisms.Methods:(1)Secured a stable transfection cell lines concluding HCT116-OE, HCT116-VC. In HCT116 cells with different expression of Rho GDI2, under different concentration of cetuximab application for 48 h. we used CCK8 、Flow cytometry and Transwell chamber test to evaluate the influence of Rho GDI2 on cells behaviors including proliferation, motility and invasion in vitro.(2) q RT-PCR and Western Blot were applied to identify the expression of E-Cadherin、Vimentin in the HCT116-OE, HCT116-VC and HCT116-NC cells.Resμlts:(1) In the treatment of cetuximab, the overexpression of Rho GDI2 enhanced the colorectal cancer cell proliferation, motility, invasion and anti-apoptosis.(2)The cell which overexpression of Rho GDI2 in the progress of epithelial-mesenchymal transition(EMT).Conclusion: The overexpression of Rho GDI2 is related to cetuximab resistance, which EMT maybe induce the resistance mechanism.