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

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

  • Chem Biol Interact. 2015 Jul 25:237:25-30. doi: 10.1016/j.cbi.2015.05.008.
Wan Daqian 1,  Wang Chuandong 2,  Qu Xinhua 1,  Ai Songtao 3,  Dai Kerong 4
Affiliations

Affiliations

  • 1 Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedics, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, PR China.
  • 2 Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine (SJTUSM) and Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS), Shanghai 200011, PR China.
  • 3 Department of Radiolog, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200011, PR China. Electronic address: draisongtao@126.com.
  • 4 Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedics, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, PR China. Electronic address: drdaikerong@126.com.
PMID: 25980584 DOI: 10.1016/j.cbi.2015.05.008
Abstract

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.

Keywords

Apoptosis; Chimaphilin; Human osteosarcoma cell lines; IGF-IR.

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