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P-糖蛋白的表达与乳腺癌和卵巢癌对阿霉素和顺铂的体内外耐药性

Expression of P-glycoprotein and in vitro or in vivo resistance to doxorubicin and cisplatin in breast and ovarian cancers.

作者信息

Veneroni S, Zaffaroni N, Daidone M G, Benini E, Villa R, Silvestrini R

机构信息

Divisione di Oncologia Sperimentale C, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy.

出版信息

Eur J Cancer. 1994;30A(7):1002-7. doi: 10.1016/0959-8049(94)90132-5.

Abstract

The expression of P-glycoprotein (P-gp) was studied by immunocytohistochemistry, using the C219 monoclonal antibody, in 39 locally advanced breast cancers and 20 ovarian cancers from previously untreated patients. P-gp was expressed in 46 and 35% of breast and ovarian tumours, respectively. A significant association was observed in both tumour types between P-gp expression and in vitro resistance to doxorubicin. We also observed a higher clinical response rate to doxorubicin +/- vincristine in patients with breast cancers not expressing P-gp. Conversely, no correlation was found between P-gp expression and in vitro resistance to cisplatin or in vivo response to cisplatin +/- cyclophosphamide treatment in ovarian cancers. Our results support the relevance of P-gp expression as a specific indicator of resistance to certain drugs, such as doxorubicin and vincristine, involved in the phenomenon of multidrug resistance in breast and ovarian cancer cells.

摘要

采用C219单克隆抗体,通过免疫细胞组织化学方法,对39例未经治疗的局部晚期乳腺癌患者和20例卵巢癌患者的P-糖蛋白(P-gp)表达情况进行了研究。P-gp分别在46%的乳腺癌和35%的卵巢癌中表达。在这两种肿瘤类型中,均观察到P-gp表达与对阿霉素的体外耐药性之间存在显著关联。我们还观察到,不表达P-gp的乳腺癌患者对阿霉素+/-长春新碱的临床缓解率更高。相反,在卵巢癌中,未发现P-gp表达与对顺铂的体外耐药性或对顺铂+/-环磷酰胺治疗的体内反应之间存在相关性。我们的结果支持P-gp表达作为对某些药物(如阿霉素和长春新碱)耐药的特异性指标的相关性,这些药物参与了乳腺癌和卵巢癌细胞的多药耐药现象。

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