Cbl-b regulates the sensitivity of cetuximab through ubiquitin-proteasome system in human gastric cancer cells.
OBJECTIVE
Cetuximab is a monoclonal antibody against epidermal growth factor receptor (EGFR) and is approved for clinical use in combination with chemotherapy in patients affected by colorectal cancer (CRC), non small cell lung cancer (NSCLC), and head and neck cancer. Compared with these cancers, gastric cancer is relatively resistant to cetuximab and its regulatory mechanism is still unclear.


METHODS
In this study, we assessed whether the ubiquitin- proteasome pathway is involved in regulating cetuximab-induced cells apoptosis in MGC803 and BGC823 gastric cancer cell lines.


RESULTS
The casitas B lineage lymphoma-b (Cbl-b), a kind of E3 ubiquitin ligase, was involved in this process. Specific silenced Cbl-b expression increased the expression of EGFR.


CONCLUSIONS
Our findings lead to a better understanding of the mechanism of cetuximab action, and suggests that Cbl-b increases the sensitivity of cetuximab in gastric cancer cells.
Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China.
Ping
P
Yu
Yibo
Y
Fan
Xiujuan
X
Qu
Jingdong
J
Zhang
Na
N
Song
Jing
J
Liu
Yunpeng
Y
Liu
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D000068818:Cetuximab / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000502:physiology; D066246:ErbB Receptors / Q000378:metabolism; D006801:Humans; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D050721:Proto-Oncogene Proteins c-cbl / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D025801:Ubiquitin; C492211:CBLB protein, human; D050721:Proto-Oncogene Proteins c-cbl; C512478:EGFR protein, human; D066246:ErbB Receptors; D046988:Proteasome Endopeptidase Complex; D000068818:Cetuximab