Insulin-like growth factor-I receptor tyrosine kinase inhibitor cyclolignan picropodophyllin inhibits proliferation and induces apoptosis in multidrug resistant osteosarcoma cell lines.

ABSTRACT: Insulin-like growth factor-I receptor (IGF-IR) is an important mediator of tumor cell survival and shows prognostic significance in sarcoma. To explore potential therapeutic strategies for interrupting signaling through this pathway, we assessed the ability of cyclolignan picropodophyllin (PPP), a member of the cyclolignan family, to selectively inhibit the receptor tyrosine kinase activity of IGF-IR in several sarcoma cell line model systems. Of the diverse sarcoma subtypes studied, osteosarcoma cell lines were found to be particularly sensitive to IGF-IR inhibition, including several multidrug resistant osteosarcoma cell lines with documented resistance to various conventional anticancer drugs. PPP shows relatively little toxicity in human osteoblast cell lines when compared with osteosa

SUBMITTER: Duan Z 

PROVIDER: S-EPMC2766237 | biostudies-literature | 2009 Aug

REPOSITORIES: biostudies-literature