Abstract: Objective To investigate the effect of cetuximab,trametinib on the proliferation and apoptosis of human colon cancer cell lines with different KRAS and BRAF genotypes in vitro and whether their combination has a synergistic effect. Methods Three different colon cancer cell lines HT29(KRAS-WT,BRAFV600 E),SW48(KRAS-WT,BRAF-WT),SW480(KRASG12 V,BRAFWT)were used,and cells of every cell line were randomly divided into control group,cetuximab group(200 μg/ml),trametinib group(1 nmol/1),cetuximab and trametinib combination group.After 72 hours of culture in vitro,the cell proliferation inhibition was detected by CCK8 assay and the apoptosis by flow cytometry of Annexin V-PI labeling assay. Results The results of cell proliferation inhibition showed that cetuximab had no significant effect on the proliferation rate of SW480 and HT-29 cells(P>0.05),but it had obvious inhibitory effect on SW48(P<0.001).Trametinib had significant proliferation inhibition effects on all three cell lines(P<0.01).The combination of the two drugs could further inhibit the proliferation of cells in three cell lines(P<0.05).The results of apoptosis showed that cetuximab alone had no effects on the apoptosis rate of the three cell lines(P>0.05).Trametinib alone had significant apoptosis-inducing effects on SW480 and HT-29(P<0.05),but not on SW48(P>0.05).Compared the combination group with the cetuximab group,the increase of apoptotic rate of HT-29 and SW480 cells was statistically significant(P<0.05),but no significant difference in the apoptosis rate of SW48(P>0.05).There was no statistical difference in the apoptotic rate between the two drug combination groups and the trametinib group(P>0.05). Conclusion The combination of cetuximab and trametinib can effectively inhibit colon cancer cell proliferation and induce apoptosis and significantly increase the drug sensitivity of KRAS and BRAF mutant human colon cancer cell lines to cetuximab,and also improve the anti-tumor effect on KRAS and BRAF wild-type colon cancer cells to some extent.The combination of the two drugs has a synergistic anti-tumor effect in vitro.