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Recombinant human PDCD5 sensitizes chondrosarcomas to cisplatin chemotherapy in vitro and in vivo

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Abstract

Clinical management of chondrosarcoma remains a challenging problem, largely due to the toxicity and resistance of this tumor to conventional chemotherapy. Programmed Cell Death 5 (PDCD5) is a protein that accelerates apoptosis in different cell types in response to various stimuli, and has been shown to be down-regulated in many cancer tissues. In this study, mRNA and protein levels of PDCD5 were found to be up-regulated in cisplatin-treated SW1353 chondrosarcoma cells compared with untreated cells. Recombinant human PDCD5 (rhPDCD5) was also shown to sensitize chondrosarcoma cells to cisplatin-based chemotherapy, with inhibition of cell growth and apoptosis detected both in vitro and in vivo. Increased expression of Bax and decreased expression of Bcl-2 were also observed, along with release of cytochrome c from mitochondria into the cytosol. Additionally, cleavage of caspase-9 and caspase-3, as well as the cleavage of poly (ADP-ribose) polymerase (PARP), were detected, suggesting that sensitization of chondrosarcoma cells involves the intrinsic mitochondrial apoptosis pathway. In vivo, the treatment of a xenograft model of chondrosarcoma with rhPDCD5 and cisplatin significantly inhibited tumor cell proliferation and induced apoptosis compared to treatment with cisplatin alone. Overall, these data provide a theoretical basis for the administration of rhPDCD5 and cisplatin for the treatment of patients with chondrosarcoma.

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Acknowledgments

This work was partly supported by the grants from the National Natural Sciences Foundation of China (30871263 and 30571870); the National Key New Drug Creation Program of China (2009ZX09102-242) and the National High Technology Research and Development Program of China (2006AA02A305).

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Authors and Affiliations

  1. Department of Orthopaedics, Peking University Third Hospital, 49 North Garden Road, Beijing, 100191, China

    Changbao Chen, Hua Zhou, Xiaoguang Liu, Zhongjun Liu & Qingjun Ma

  2. Peking University Center for Human Disease Genomics, 38 Xueyuan Road, Beijing, 100191, China

    Lanjun Xu, Dong Xu, Ying Wang, Yingmei Zhang, Dalong Ma & Yingyu Chen

  3. Laboratory of Medical Immunology, School of Basic Medical Sciences, Peking University, 38 Xueyuan Road, Beijing, 100191, China

    Lanjun Xu, Dong Xu, Ying Wang, Yingmei Zhang, Dalong Ma & Yingyu Chen

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  1. Changbao Chen
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  2. Hua Zhou
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  3. Lanjun Xu
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  4. Dong Xu
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  10. Qingjun Ma
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Correspondence to Qingjun Ma or Yingyu Chen.

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Chen, C., Zhou, H., Xu, L. et al. Recombinant human PDCD5 sensitizes chondrosarcomas to cisplatin chemotherapy in vitro and in vivo. Apoptosis 15, 805–813 (2010). https://doi.org/10.1007/s10495-010-0489-5

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  • DOI: https://doi.org/10.1007/s10495-010-0489-5

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