关于顺铂与去配体白蛋白结合以提高其抗肿瘤活性并降低全身毒性作用可能性的研究。

The study of possibility to elevate antitumor activity and decrease of systemic toxic effects of cisplatin by its binding with deliganded albumin.

作者信息

Sakhno L A, Sarnatskaya V V, Yushko L A, Melnikov O R, Momot V Ya, Korneeva L N, Svintsiskiy V S, Korotich V G, Nechitaylo I I, Nikolaev V G

机构信息

Department of Physico-chemical Mechanisms of Sorption Detoxification, R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NAS of Ukraine, Kyiv, Ukraine.

出版信息

Exp Oncol. 2006 Dec;28(4):303-7.

PMID:17285115

Abstract

AIM

To evaluate antitumor and toxic action of cisplatin (CP) in non-bound form and in a complex with deliganded albumin.

METHODS

To study complex-formation between CP and albumin, differential scanning and isothermic flow microcalorimetry were used. For quantitive evaluation of albumin-bound CP, the method of ultrafiltration was applied. Concentration of platinum in the samples was determined by atomic-absorption spectral analysis. Antitumor and toxic effect of CP and CP-albumin complex was studied in vivo using Guerin carcinoma (GC) model.

RESULTS

It has been shown that the second drug-binding site, located in the III domain of albumin molecule is one of the main points of binding of CP. Purification of officinal human serum albumin (HSA) on highly active carbon hemosorbents of HSGD mark allows to obtain deliganded albumin (dHSA) with elevated complex-forming ability toward CP. Administration of CP-dHSA complex provides higher rate of GC growth inhibition, than that of CP, and the content of creatinine in blood plasma of GC-bearing rats increases by 15% versus 40% in the case of CP administration.

CONCLUSION

The data obtained allow recommend application of CP-dHSA to complex for enhancement of antitumor action and decrease of toxic effects of cisplatin.

摘要

目的

评估非结合形式和顺铂（CP）与去配体白蛋白复合物的抗肿瘤及毒性作用。

方法

采用差示扫描量热法和等温流动微量热法研究CP与白蛋白之间的络合形成。应用超滤法对结合白蛋白的CP进行定量评估。通过原子吸收光谱分析测定样品中铂的浓度。使用格林氏癌（GC）模型在体内研究CP和CP-白蛋白复合物的抗肿瘤及毒性作用。

结果

已表明位于白蛋白分子III结构域的第二个药物结合位点是CP的主要结合点之一。在HSGD标记的高活性碳血液吸附剂上纯化药用人类血清白蛋白（HSA），可得到对CP具有更高络合形成能力的去配体白蛋白（dHSA）。给予CP-dHSA复合物比给予CP能提供更高的GC生长抑制率，且荷GC大鼠血浆中肌酐含量增加15%，而给予CP时增加40%。