The insulin-like growth factor I receptor/insulin receptor tyrosine kinase inhibitor PQIP exhibits enhanced antitumor effects in combination with chemotherapy against colorectal cancer models

胰岛素样生长因子 I 受体/胰岛素受体酪氨酸激酶抑制剂 PQIP 与化疗联合治疗结直肠癌模型,表现出增强的抗肿瘤作用

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作者:Sara A Flanigan, Todd M Pitts, S Gail Eckhardt, John J Tentler, Aik Choon Tan, Andrew Thorburn, Stephen Leong

Conclusions

Combination treatment with PQIP, the dual IGF-IR/insulin receptor tyrosine kinase inhibitor, and standard colorectal cancer chemotherapy resulted in enhanced antiproliferative effects against colorectal cancer cell line models, providing a scientific rationale for the testing of OSI-906 and standard colorectal cancer treatment regimens.

Purpose

There is growing evidence implicating the importance of the insulin-like growth factor (IGF) pathway in colorectal cancer based upon the

Results

Treatment with the combination of PQIP and each of three chemotherapies resulted in an enhanced decrease in proliferation of all four colorectal cancer cell lines compared with single-agent treatment. This inhibition was not associated with a significant induction of apoptosis, but was accompanied by cell cycle arrest and changes in phosphorylation of Akt. Interestingly, antitumor activity between PQIP and SN-38 in vitro was also reflected in the human colorectal cancer xenograft model. Conclusions: Combination treatment with PQIP, the dual IGF-IR/insulin receptor tyrosine kinase inhibitor, and standard colorectal cancer chemotherapy resulted in enhanced antiproliferative effects against colorectal cancer cell line models, providing a scientific rationale for the testing of OSI-906 and standard colorectal cancer treatment regimens.

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