Inhibition of the insulin-like growth factor 1 receptor pathway enhances the antitumor effect of cisplatin in human malignant mesothelioma cell lines.
Human malignant mesothelioma (HMM) is a fatal tumor and is poorly responsive to current therapeutic regimens. The insulin-like growth factor 1 receptor (IGF-1R) pathway is activated in HMM cell lines and tissues. Treatment with AG1024, an inhibitor of the IGF-1R pathway, significantly decreased cell proliferation and attenuated the phosphorylation of Akt and p44/42. In addition, it significantly enhanced the cytotoxic effects of cisplatin in HMM cell lines. This study supports the conjecture that inhibition of the IGF-1R pathway may be a useful target for reducing toxicity and alleviating chemoresistance to traditional anticancer drugs in HMM patients.
Kai
Kiyonori
K
Department of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, 4700 Hillsborough Street, Raleigh, NC 27606, USA.
D'Costa
Susan
S
Sills
Robert C
RC
Kim
Yongbaek
Y
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor / Q000187:drug effects; D002945:Cisplatin / Q000627:therapeutic use*; D006801:Humans; D008654:Mesothelioma / Q000188:drug therapy*; D010997:Pleural Neoplasms / Q000188:drug therapy; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors*; D015398:Signal Transduction / Q000187:drug effects; D020032:Tyrphostins / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D020032:Tyrphostins; C447031:tyrphostin AG 1024; D017526:Receptor, IGF Type 1; D002945:Cisplatin