Cetuximab inhibits gastric cancer growth in vivo, independent of KRAS status.
Mutation status of Kirsten rat sarcoma viral oncogene homolog (KRAS) may serve as a negative predictive marker of Cetuximab in treating colorectal cancer. The present study was to determine the role of KRAS status in EGFR antibody treatment for gastric cancer. KRAS status was clarified in SGC-7901 (wild type) and YCC-2 (G→A mutation) gastric cancer cell lines. Anti-proliferative and pro-apoptotic effects of Cetuximab were tested both in vitro and in vivo, the expression of phosphorylated (p) ERK, a downstream protein in EGFR-RAS-MEK pathway, was also analyzed. No significant in vitro anti-proliferative or pro-apoptotic effects of Cetuximab were observed in both cell lines. The growth of either SGC-7901 or YCC-2 gastric cancer xenograft was significantly inhibited by Cetuximab. Apoptosis was induced in SGC-7901 but not in YCC-2 xenografts after Cetuximab treatment. The expression of pERK was up-regulated in YCC-2 but not SGC-7901 xenografts after Cetuximab treatment. In conclusion, KRAS (G→A) mutation does not affect in vivo anti-cancer efficacy of Cetuximab.
Min
M
Shi
Hailong
H
Shi
Jun
J
Ji
Qu
Q
Cai
Xuehua
X
Chen
Yingyan
Y
Yu
Bingya
B
Liu
Zhenggang
Z
Zhu
Departments of Surgery and Clinical Oncology, Shanghai Institute of Digestive Surgery, Rui Jin Hospital, Shanghai Jiaotong University School of Medicine, No. 197 Ruijin Er Road, Shanghai 200025, China. jun_zj10977@163.com.
Jun
J
Zhang
D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D000068818:Cetuximab; D004305:Dose-Response Relationship, Drug; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D008297:Male; D008819:Mice, Nude; D009154:Mutation; D010766:Phosphorylation; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D015398:Signal Transduction / Q000187:drug effects; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D013997:Time Factors; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays; D018631:ras Proteins / Q000235:genetics*
D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; C512478:EGFR protein, human; D066246:ErbB Receptors; D048049:Extracellular Signal-Regulated MAP Kinases; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D000068818:Cetuximab