乳腺癌细胞赫赛汀耐药的发展。
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Kute T, Lack CM, Willingham M, Bishwokama B, Williams H, Barrett K, Mitchell T, Vaughn JP
乳腺癌细胞赫赛汀耐药的发展。
细胞检测A. 2004 Feb;57(2):86-93。
- PubMed ID
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14750129 (PubMed视图]
- 摘要
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背景:赫赛汀(Herceptin)是一种HER-2人源抗体，目前在临床上用于转移性乳腺癌的治疗。HER-2+患者的有效率仅为30%，对耐药机制知之甚少。赫赛汀的作用机制也不清楚，但与细胞周期抑制有关。方法:采用细胞计数和细胞周期分析方法，观察赫赛汀及其他抗体治疗的效果。流式细胞仪检测HER-2和p27表达水平，Western blot检测活化AKT水平。免疫荧光法检测细胞HER-2和p27的表达。结果:赫赛汀治疗BT-474细胞可抑制细胞生长并阻滞在G1期。生长抑制的疗效与Her-2抗体的结合亲和力没有直接关系。我们的实验室已经开发出对赫赛汀治疗有抗性的细胞系。在耐药细胞系中，抗体的结合不受阻碍。 However, Herceptin has completely lost the ability to inhibit cell proliferation. Yet, the mouse isotype 4D5 maintains significant inhibitory activity upon Herceptin-resistant clones. CONCLUSIONS: Herceptin binds effectively to Her-2 on the cell surface of Herceptin-resistant cell lines and the level of Her-2 expression on the cell surface is not downregulated. Herceptin resistance is not due to downregulation of levels of AKT protein expression, although, phosphorylation of AKT is enhanced in resistant lines and could have a role in resistance. Resistance appears to correlate with the loss of nuclear expression of the cyclin-dependent kinase inhibitor, p27, as defined by immunofluorescence and flow cytometry studies and cdk-2 binding studies.
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