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转铁蛋白-阿霉素偶联物治疗膀胱癌潜力的评估

Evaluation of the potential of transferrin-adriamycin conjugates in the treatment of bladder cancer.

作者信息

Munns J, Yaxley J, Coomer J, Lavin M F, Gardiner R A, Watters D

机构信息

Royal Brisbane Hospital, Queensland, Australia.

出版信息

Br J Urol. 1998 Aug;82(2):284-9. doi: 10.1046/j.1464-410x.1998.00736.x.

Abstract

OBJECTIVE

To assess the ability of a transferrin-adriamycin conjugate (Tf-ADR) to target transferrin receptor (TfR)-positive cancer cells selectively and to overcome drug resistance in bladder cancer cell lines.

MATERIALS AND METHODS

Two paired sets of cell lines were used: the first was Chinese hamster ovary (CHO) cells (TfR-negative TRVb cells, as a model for normal resting cells, and TRVb-1 cells which were transfected with human TfR), and the second was a pair of bladder cancer cell lines (ADR-sensitive MGH-U1 cells and ADR-resistant MGH-U1R cells). Cell survival curves were determined after treatment with ADR, Tf and Tf-ADR.

RESULTS

MGH-U1, TRVb and TRVb-1 cells required similar concentrations of ADR and Tf-ADR for 50% inhibition of growth; MGH-U1R cells were resistant to both ADR and TF-ADR.

CONCLUSION

Tf-ADR did not prevent toxicity to the TfR-negative cells nor did it overcome the resistance of the ADR-resistant cells. These results imply that Tf-ADR does not provide a better cytotoxic drug delivery system for the treatment of bladder cancer.

摘要

目的

评估转铁蛋白 - 阿霉素偶联物(Tf - ADR)选择性靶向转铁蛋白受体(TfR)阳性癌细胞以及克服膀胱癌细胞系耐药性的能力。

材料与方法

使用两组配对的细胞系:第一组是中国仓鼠卵巢(CHO)细胞(TfR阴性的TRVb细胞,作为正常静息细胞的模型,以及转染了人TfR的TRVb - 1细胞),第二组是一对膀胱癌细胞系(阿霉素敏感的MGH - U1细胞和阿霉素耐药的MGH - U1R细胞)。用阿霉素、转铁蛋白和Tf - ADR处理后测定细胞存活曲线。

结果

MGH - U1、TRVb和TRVb - 1细胞对生长抑制率达50%时所需的阿霉素和Tf - ADR浓度相似;MGH - U1R细胞对阿霉素和TF - ADR均耐药。

结论

Tf - ADR并未防止对TfR阴性细胞的毒性作用,也未克服阿霉素耐药细胞的耐药性。这些结果表明,Tf - ADR并未为膀胱癌治疗提供更好的细胞毒性药物递送系统。

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