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学科主题临床医学
Diammine dicarboxylic acid platinum enhances cytotoxicity in platinum-resistant ovarian cancer cells through induction of apoptosis and S-phase cell arrest
Zheng, Hong1,4; Hu, Wei1; Yu, Dongfang2; Shen, De-Yu1; Fu, Siqing3; Kavanagh, John J.1; Wei, I-Chien2; Yang, David J.2
关键词CDDP CDDP analogue drug resistance ovarian cancer
刊名PHARMACEUTICAL RESEARCH
2008-10-01
DOI10.1007/s11095-008-9621-4
25期:10页:2272-2282
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Chemistry, Multidisciplinary ; Pharmacology & Pharmacy
研究领域[WOS]Chemistry ; Pharmacology & Pharmacy
关键词[WOS]IN-VITRO ; CLINICAL IMPLICATIONS ; CISPLATIN-RESISTANT ; DRUG-DELIVERY ; CHEMOTHERAPY ; ACTIVATION ; POLYSACCHARIDES ; CHITOSAN ; VIVO
英文摘要

Purpose. Polysaccharides such as chondroitin play a potent role in tumor growth, tissue repair and angiogenesis. These properties make chondroitin a good candidate for novel drug delivery systems. Diammine dicarboxylic acid platinum (DDAP), a novel polymeric platinum compound, was developed by conjugating the platinum analogue to aspartate-chondroitin for drug delivery to tumor cells. DDAP improves platinum solubility which may reduce systemic toxicity and be more efficacious than cisplatin in killing tumor cells.

Methods. We tested and compared the cytotoxic effects of DDAP and CDDP on the platinum-sensitive 2008 and A2780 ovarian cancer cell lines and their platinum-resistant sublines 2008.C13 and A2780cis; we also investigated DDAP′s mechanism of action.

Results. In the platinum-sensitive cell lines, the cytotoxic effects of DDAP and CDDP were comparable. However, in the platinum-resistant sublines, significantly greater cell-growth inhibition was induced by DDAP than by CDDP, especially at lower doses. DDAP also induced more apoptosis than CDDP did in the 2008.C13 subline, which was partially mediated by the caspase 3-dependent pathway. In addition, lower (but not higher) doses of DDAP arrested 90% of S-phase 2008.C13 cells, which might be associated with up-regulation of p21 and maintenance of low cyclin A expression. Furthermore, greater cellular uptake of DDAP was seen in platinum-resistant than in platinum-sensitive ovarian cancer cells.

Conclusions. Low-dose DDAP enhances drug delivery to platinum-resistant ovarian cancer cells and substantially inhibits their growth by inducting apoptosis and arresting cells in the S-phase, suggesting that DDAP may overcome platinum resistance in ovarian cancer.

语种英语
WOS记录号WOS:000259187800008
项目编号5P30CA016672-32
资助机构M. D. Anderson&prime ; s institutional grant and Core Grant
引用统计
被引频次:4[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/64921
专题北京大学临床肿瘤学院_妇科肿瘤科
作者单位1.Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol, Houston, TX 77030 USA
2.Univ Texas MD Anderson Canc Ctr, Dept Expt Diagnost Imaging, Houston, TX 77030 USA
3.Univ Texas MD Anderson Canc Ctr, Dept Gynecol Med Oncol, Houston, TX 77030 USA
4.Beijing Canc Hosp, Dept Gynecol, Beijing 100036, Peoples R China
推荐引用方式
GB/T 7714
Zheng, Hong,Hu, Wei,Yu, Dongfang,et al. Diammine dicarboxylic acid platinum enhances cytotoxicity in platinum-resistant ovarian cancer cells through induction of apoptosis and S-phase cell arrest[J]. PHARMACEUTICAL RESEARCH,2008,25(10):2272-2282.
APA Zheng, Hong.,Hu, Wei.,Yu, Dongfang.,Shen, De-Yu.,Fu, Siqing.,...&Yang, David J..(2008).Diammine dicarboxylic acid platinum enhances cytotoxicity in platinum-resistant ovarian cancer cells through induction of apoptosis and S-phase cell arrest.PHARMACEUTICAL RESEARCH,25(10),2272-2282.
MLA Zheng, Hong,et al."Diammine dicarboxylic acid platinum enhances cytotoxicity in platinum-resistant ovarian cancer cells through induction of apoptosis and S-phase cell arrest".PHARMACEUTICAL RESEARCH 25.10(2008):2272-2282.
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