Zhang Bingchang, Luo Haiqing, Xu Qinjuan, Lin Lirong, Zhang Bing
School of Medicine, University of Xiamen, Xiamen, 361102, P. R. China.
College of Chemistry and Chemical Engineering, University of Xiamen, Xiamen, 361005, P. R. China.
Oncotarget. 2017 Feb 21;8(8):13620-13631. doi: 10.18632/oncotarget.14620.
The development of transition-metal-based antitumor drug candidates increases the metallopharmaceuticals study dramatically. Two trans-thiosemicarbazone-based, Schiff base palladium (Pd) (II) complexes, DMABTSPd (TSPd) and DMABPTSPd (PTSPd), were prepared and characterized as described in our previous study. Here, we investigated whether the two complexes have antitumor effect on human gastric adenocarcinoma cell lines, BGC-823 and SGC-7901, compared with normal human gastric mucosal epithelial cell line, Ges-1. The results show that the Pd complex with the bare amino group (DMABTSPd(TSPd)) can inhibit cell viabilities and induce apoptosis in human gastric carcinoma cells, rather than the Pd complex without the bare amino group (DMABPTSPd (PTSPd)). This occurs via a mitochondrial-related pathway by down-regulating the level of Bcl-2 expression and up-regulating the level of Bid expression. Meanwhile, DMABTSPd (TSPd) suppressed tumor growth via a mitochondrial-related pathway in a nude mouse tumor xenograft model derived from BGC-823 cells. These findings demonstrate that DMABTSPd (TSPd) is worthy of further structural optimization and representing a promising Pd complex for the development of a new antitumor therapeutic agent.
基于过渡金属的抗肿瘤候选药物的发展极大地推动了金属药物的研究。如我们之前的研究所描述，制备并表征了两种基于反式硫代半卡巴腙的席夫碱钯（Pd）（II）配合物，即DMABTSPd（TSPd）和DMABPTSPd（PTSPd）。在此，我们研究了与正常人胃黏膜上皮细胞系Ges-1相比，这两种配合物对人胃腺癌细胞系BGC-823和SGC-7901是否具有抗肿瘤作用。结果表明，带有游离氨基的钯配合物（DMABTSPd（TSPd））能够抑制人胃癌细胞的活力并诱导其凋亡，而不带游离氨基的钯配合物（DMABPTSPd（PTSPd））则不然。这是通过下调Bcl-2表达水平和上调Bid表达水平，经由线粒体相关途径发生的。同时，在源自BGC-823细胞的裸鼠肿瘤异种移植模型中，DMABTSPd（TSPd）通过线粒体相关途径抑制肿瘤生长。这些发现表明，DMABTSPd（TSPd）值得进一步进行结构优化，是开发新型抗肿瘤治疗药物的一种有前景的钯配合物。
