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

• DOI: 10.1007/s10495-010-0489-5
• Publication Date: 2010-03-26T11:37:45Z
• Authors: Changbao Chen; Hua Zhou; Lanjun Xu; Dong Xu; Ying Wang; Yingmei Zhang; Xiaoguang Liu; Zhongjun Liu; Dalong Ma; Qingjun Ma; Yingyu Chen
• Keywords: 0301 basic medicine; Mice, Inbred BALB C; 0303 health sciences; Chondrosarcoma; Cytochromes c; Mice, Nude; Apoptosis; Bone Neoplasms; Xenograft Model Antitumor Assays; Recombinant Proteins; Neoplasm Proteins; 3. Good health; Mice; 03 medical and health sciences; Cell Line, Tumor; Antineoplastic Combined Chemotherapy Protocols; Animals; Humans; Female; Cisplatin; Apoptosis Regulatory Proteins; bcl-2-Associated X Protein

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.