Chimaphilin inhibits proliferation and induces apoptosis in multidrug resistant osteosarcoma cell lines through insulin-like growth factor-I receptor (IGF-IR) signaling

•Chimaphilin inhibited the growth of human osteosarcoma cell lines.•Chimaphilin can inhibit the receptor tyrosine kinase activity of IGF-IR.•Chimaphilin can increase the sensitivity in doxorubicin-resistant cell lines.•Knockdown of IGF-IR cause resensitization to doxorubicin in drug-resistant cells....

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Bibliographic Details
Published in:Chemico-biological interactions 2015-07, Vol.237, p.25-30
Main Authors: Daqian, Wan, Chuandong, Wang, Xinhua, Qu, Songtao, Ai, Kerong, Dai
Format: Article
Language:English
Subjects:
Apoptosis
Apoptosis - drug effects
Bone Neoplasms - metabolism
Bone Neoplasms - pathology
Cell Line, Tumor
Cell Proliferation - drug effects
Chimaphilin
Drug Resistance, Neoplasm
Human osteosarcoma cell lines
Humans
IGF-IR
Naphthoquinones - pharmacology
Osteosarcoma - metabolism
Osteosarcoma - pathology
Receptor, IGF Type 1 - metabolism
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Summary:•Chimaphilin inhibited the growth of human osteosarcoma cell lines.•Chimaphilin can inhibit the receptor tyrosine kinase activity of IGF-IR.•Chimaphilin can increase the sensitivity in doxorubicin-resistant cell lines.•Knockdown of IGF-IR cause resensitization to doxorubicin in drug-resistant cells. Chimaphilin, an active compound separated from pyrola, possesses the highly efficient antitumor activities. Insulin-like growth factor-I receptor (IGF-IR) plays an important role in tumor cell survival. To look for effective strategies for interrupting IGF-IR signaling pathway, we found that chimaphilin can inhibit the receptor tyrosine kinase activity of IGF-IR. Chimaphilin inhibited the growth of both drug-sensitive and drug-resistant osteosarcoma cell lines in a time and dose-dependent manner; however, it showed relatively little toxicity in normal osteoblast cell lines. Chimaphilin can increase the sensitivity of doxorubicin in doxorubicin-resistant osteosarcoma cell lines. Additionally, small interfering RNA downregulation of IGF-IR expression in drug-resistant cell lines also caused resensitization to doxorubicin. Above all, we conclude that chimaphilin represents a valuable natural source and may potentially be applicable for reversing the drug-resistant phenotype in osteosarcoma therapy.
ISSN:0009-2797
1872-7786
DOI:10.1016/j.cbi.2015.05.008