E-poster Presentation 2014 World Cancer Congress

KRAS mutation does not influence anti-proliferation effects but inhibits apoptosis of cetuximab in gastric xenografts (#1142)



Kirsten rat sarcoma viral oncogene homolog (KRAS) status influences the efficacy of cetuximab in treating metastatic colorectal cancer. Yet, its role in gastric cancer is uncertain.


The aim of this study is to evaluate the impacts of KRAS status on the efficacy of cetuximab in treating gastric cancer cells both in vitro and in vivo.


KRAS wild-type (WT) gastric cancer cells SGC-7901 and mutant-type (MT) gastric cancer cells YCC-2 were identified, both cells express epithelial growth factor receptor (EGFR) protein.  


No significant in vitro growth inhibitory (2.4%±3.2% and 1.4%±1.7%) and apoptosis induction (0.38%±0.16% and 3.28%±1.23%) of cetuximab were observed in both cell lines. Compared with control group, cetuximab obviously inhibited the growth of both SGC-7901 (p=0.0028) and YCC-2 (p=0.014) xenografts, but more significant in SGC-7901 xenografts. The results of immunohistochemistry staining of Ki-67 demonstrated that cell proliferation was significantly decreased both in SGC-7901(80% vs 30%) and YCC-2 (50% vs 10%) xenografts. Apoptic index (AI) in SGC-7901 xenografts of cetuximab treatment group was significantly increased (17.4%±2.6% vs 5.4%±1.4%, p=0.002) than that in control group. However, AI in YCC-2 xenografts, which was KRAS mutant, was not significantly changed (4.6%±1.1% vs 6.0%±1.4%, p=0.123) after cetuximab treatment. Phosphorylated ERK (p-ERK), which was involved in apoptosis resistance, was up-regulated in cetuximab treatment group of YCC-2 xenografts, but not obviously in SGC-7901 xenografts.


KRAS mutation does not influence the anti-proliferation efficacy of cetuximab in vivo, but may involve the apoptic resistance via up-regulation of p-ERK. These results may enrich the mechanism exploration of cetuximab resistance in gastric cancer.