Effect of Simvastatin on Cetuximab Resistance in Human Colorectal Cancer With KRAS Mutations
作者： Jeeyun Lee , Inkyoung Lee , Boram Han , Joon Oh Park , Jiryeon Jang
DOI: 10.1093/JNCI/DJR070
关键词:
摘要: BACKGROUND Metastatic colorectal cancer (CRC) patients with v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations are resistant to treatment cetuximab, a monoclonal antibody that targets the epidermal growth factor receptor. Statins have reported antitumor activity, but it is unknown whether simvastatin can reverse cetuximab resistance in KRAS mutant CRC. METHODS Human CRC cell lines (LS153, LS174T, DLD1, LoVo, SW403, SW480, SNU175, and LS1034) or v-raf murine B1 (BRAF) (DiFi, SW48, HT29, RKO) were used test effect of simvastatin, plus on proliferation apoptosis vitro. Because BRAF(V600E) may be responsible for wild-type cells, we measured xenograft tumors originating from BRAF cells mice treated alone (n = 5 per group). We immunoblot assays study RAS-regulated activation protein after treatment. All statistical tests two-sided. RESULTS Addition (0.2 μM) (0.03-1.0 reduced (P < .001) not Treatment activity induced apoptosis. compared (eg, DLD1 vs + mean tumor volume 49.4 20.2 cm(3), difference 29.2 95% confidence interval 19.7 38.5, P .001); combination had no tumors. CONCLUSION Simvastatin overcome colon by modulating inducing
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