Background:
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.
Aim:
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.
Methods:
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.
Results:
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.
Conclusions:
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.