Recombinant human PDCD5 sensitizes chondrosarcomas to cisplatin chemotherapy in vitro and in vivo
Recombinant human PDCD5 sensitizes chondrosarcomas to cisplatin chemotherapy in vitro and in vivo
复制标题
重组人PDCD5在体外和体内使软骨肉瘤对顺铂化疗敏感
DOI：
10.1007/s10495-010-0489-5
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发表时间：
2010-07-01
期刊：
影响因子：
7.2
通讯作者：
Chen, Yingyu
中科院分区：
文献类型：
--
作者：
Chen, Changbao;Zhou, Hua;Chen, Yingyu
软骨肉瘤的临床治疗仍然是一个具有挑战性的问题，主要是由于这种肿瘤对常规化疗的毒性和耐药性。程序性细胞死亡5（PDCD 5）是一种蛋白质，其响应于各种刺激而加速不同细胞类型中的凋亡，并且已显示在许多癌症组织中下调。在这项研究中，PDCD 5的mRNA和蛋白水平被发现在顺铂处理的SW 1353软骨肉瘤细胞与未经处理的细胞相比，上调。重组人PDCD 5（rhPDCD 5）也被证明是敏感的软骨肉瘤细胞顺铂为基础的化疗，抑制细胞生长和凋亡检测在体外和体内。Bax的表达增加，Bcl-2的表达减少，沿着细胞色素c从线粒体释放到胞质溶胶中。此外，caspase-9和caspase-3的裂解，以及多聚（ADP-核糖）聚合酶（PARP）的裂解，被检测到，这表明软骨肉瘤细胞的致敏涉及内在的线粒体凋亡途径。在体内，与单独用顺铂治疗相比，用rhPDCD 5和顺铂治疗软骨肉瘤异种移植模型显著抑制肿瘤细胞增殖并诱导细胞凋亡。这些数据为rhPDCD 5联合顺铂治疗软骨肉瘤提供了理论依据。
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.