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新型钯(II)和铂(II)配合物对非小细胞肺癌细胞的体外细胞死亡诱导作用。

Cell death-inducing effect of novel palladium(II) and platinum(II) complexes on non-small cell lung cancer cells in vitro.

机构信息

Department of Clinical Biochemistry, Medical School, Uludag University, 16059, Bursa, Turkey.

出版信息

J Cancer Res Clin Oncol. 2011 Oct;137(10):1425-34. doi: 10.1007/s00432-011-1021-1. Epub 2011 Aug 2.

Abstract

PURPOSE

Treatment for lung cancer is still far from satisfying rates. Therefore, there is a need for novel anticancer agents. For this purpose, novel platinum and palladium complexes {Pd(sac)(terpy)·4H(2)O (Complex 1), Pt(sac)(terpy)·5H(2)O (Complex 2), PdCl(terpy)·2H(2)O (Complex 3), PtCl(terpy)·2H(2)O (Complex 4)} have been tested against three different non-small cell lung cancer cell lines (A549, H1299, PC-3).

METHODS

Growth-inhibiting effects have been tested by the MTT and ATP viability assays. Apoptosis has been detected by the caspase-cleaved cytokeratin 18 (M30-antigen) assay. Necrosis has been detected by staining the cells with fluorescent dyes. Mitotic index has been calculated by counting the mitotic figures after staining with hematoxylin.

RESULTS

The complex 3 exhibited significant anti-growth effects, and its anti-growth effect was more powerful than that of cisplatin that is a standard chemotherapeutic agent for this type of cancer. The complexes did not induce apoptosis, while necrosis clearly took place.

CONCLUSIONS

Novel Pd(II) complex (PdCl(terpy)·2H(2)O) seems to represent a potentially active drug against non-small cell lung cancer cell lines, and further studies in vivo are warranted.

摘要

目的

肺癌的治疗效果仍远不尽如人意。因此,需要新型抗癌药物。为此,我们合成了新型铂和钯配合物Pd(sac)(terpy)·4H(2)O(配合物 1)、Pt(sac)(terpy)·5H(2)O(配合物 2)、PdCl(terpy)·2H(2)O(配合物 3)和PtCl(terpy)·2H(2)O(配合物 4),并测试了它们对三种不同的非小细胞肺癌细胞系(A549、H1299、PC-3)的抑制作用。

方法

采用 MTT 和 ATP 活力测定法检测生长抑制作用。通过半胱氨酸天冬氨酸蛋白酶 3 切割细胞角蛋白 18(M30 抗原)检测凋亡。通过荧光染料染色检测坏死。通过对苏木精染色的细胞进行计数来计算有丝分裂指数。

结果

配合物 3 表现出显著的抗增殖作用,其抗增殖作用强于顺铂,顺铂是治疗这种癌症的标准化疗药物。这些配合物不诱导细胞凋亡,但明显诱导细胞坏死。

结论

新型 Pd(II)配合物PdCl(terpy)·2H(2)O 似乎对非小细胞肺癌细胞系具有潜在的活性,有必要进行进一步的体内研究。

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