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Lentivirus-mediated RNAi knockdown of insulin-like growth factor-1 receptor inhibits growth, reduces invasion, and enhances radiosensitivity in human osteosarcoma cells

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Abstract

The type 1 insulin-like growth factor receptor (IGF-1R) is essential for tumorigenicity, tumor proliferation, and protection from apoptosis. IGF-1R overexpression has been found in many human cancers including osteosarcoma. To explore its possibility as a therapeutic target for the treatment of osteosarcoma, lentivirus-mediated siRNA was employed to downregulate endogenous IGF-1R expression to study the function of IGF-1R in tumorigenesis and radioresistance of osteosarcoma cells. The IGF-1R expression was persistently and markedly reduced by lentivirus-mediated RNAi. Downregulation of IGF-1R expression in osteosarcoma cells significantly suppressed their growth rates in vitro and reduced the potential of tumorigenicity in vivo. Moreover, the specific downregulation arrested cells in G0/G1 phase of cell cycle and also induced apoptosis which correlated with the activation of Caspase-3. Furthermore, we also observed that suppression of IGF-1R could reduce the invasiveness of osteosarcoma cells and enhance their radiosensitivity. Our study suggested that lentivirus-mediated RNAi silencing targeting IGF-1R could induce potent antitumor activity and radiosensitizing activity in human osteosarcomas.

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Acknowledgment

We are very grateful for the sincere help and technical support by Department of Biochemistry in Nanjing Medicine University

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, Nanjing Medical University, Hanzhong Road 140, 210029, Nanjing, Jiangsu Province, People’s Republic of China

    Yin-He Wang & Wei De

  2. Bone and Stem Cell Centre, Nanjing Medical University, 210029, Nanjing, Jiangsu Province, People’s Republic of China

    Deng-Shun Miao

  3. Department of Orthopaedic Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, 210001, Nanjing, People’s Republic of China

    Yin-He Wang, Yong Qiu, Jin Xiong & Yi-Xin Chen

  4. Department of Oncology, The Second Affiliated Hospital of Nanjing Medical University, 210011, Nanjing, China

    Zhao-Xia Wang

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  1. Yin-He Wang
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  2. Zhao-Xia Wang
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  3. Yong Qiu
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  4. Jin Xiong
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  5. Yi-Xin Chen
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  6. Deng-Shun Miao
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  7. Wei De
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Corresponding author

Correspondence to Wei De.

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Y.-H. Wang and Z.-X. Wang should be regarded as joint first authors for their equal contributions.

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Wang, YH., Wang, ZX., Qiu, Y. et al. Lentivirus-mediated RNAi knockdown of insulin-like growth factor-1 receptor inhibits growth, reduces invasion, and enhances radiosensitivity in human osteosarcoma cells. Mol Cell Biochem 327, 257–266 (2009). https://doi.org/10.1007/s11010-009-0064-y

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  • DOI: https://doi.org/10.1007/s11010-009-0064-y

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