The Effect On Colorectal Cancer Cell Lines Of Combined Sunitinib And Cetuximab Treatment

Object: Study the synergistic effects of sunitinib combined with cetuximab on K-raswild-type and mutant-type human colorectal cancer cell lines.Methods: The anti-proliferative and cell cycle arrest effect of cetuximab and sunitinibas single agents or in combination for treatment of the K-ras wild-type humancolorectal cancer cell line HCT-8and the mutant-type HCT-116cell line wereevaluated using the MTT assay and flow cytometry.Results: There were time-dependent and dose-dependent growth inhibitory effects ofcetuximab and sunitinib as single agents for the HCT-8cell line. The reduced cellgrowth with exposure to sunitinib was significant (P<0.05). In the HCT-116cells,proliferation was decreased with increased concentrations and exposure time tosunitinib (P<0.05) but not to cetuximab (P＞0.05). In combination treatment, theproliferation of HCT-8cells was decreased with the increase of concentrations andtime of exposure (P<0.05). In the HCT-116cells growth was inhibited with increasedconcentrations and time of exposure increased, but growth inhibition was was notdependent on the concentration and exposure time of cetuximab. Flow cytometryassay showed that with single drug treatment, the proportion of cells in S phase wasreduced in the HCT-116groups as the suntinib concentration increased, the number ofcells in S phase approached zero with increasing concentrations; there wasstatistically significant differences between the different concentrations of suntinib(P<0.01). There was no change in the proportion of cells in S phase with increasingconcentrations of cetuxmab (P>0.05). With combination therapy, the proportion ofcells in S phase was reduced in HCT-116groups with the increased suntinibconcentration, and the proportion of S phase cells approached zero. There was againa statistically significant differences between suntinib concentrations (P<0.01), but there were no changes in the proportion of cells in S phase when differentconcentrations of cetuxmab were used.Conclusion: The wild-type HCT-8cell lines is sensitive to cetuximab as well assunitinib, there is synergistic effect on the combination with these two drugs. Themutant K-ras HCT-116cell line is resistant to cetuximab. Cetuximab has no effect onthe cell cycle of the K-ras mutant HCT-116lines, but sunitinib can arrest theHCT-116cell line in S phase.