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鉴定β2-微球蛋白作为卵巢癌的一个潜在靶点。

Identification of beta2-microglobulin as a potential target for ovarian cancer.

机构信息

State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan, China.

出版信息

Cancer Biol Ther. 2009 Dec;8(24):2323-8. doi: 10.4161/cbt.8.24.9982. Epub 2009 Dec 2.

DOI:10.4161/cbt.8.24.9982
PMID:19829086
Abstract

Ovarian cancer is one of the most lethal gynecological cancers. Antibody-based therapy has emerged as an important therapeutic approach for an increasing number of malignancies. Here, we prepared an antibody pool against SKOV3 ovarian cancer cells, which could induce apoptosis of SKOV3 cells in a dose- and time-dependent manner. Through SEREX analysis, beta 2-microglobulin (b2M) was identified as the potential target molecules of functional antibodies. The immune IgG (i-IgG) of antibody pool had little effects on other kinds of cancer cells, maybe because of the more secretion of b2M by SKOV3. Further studies indicated that specific antibody of b2M indeed also can inhibit the growth of SKOV3. In addition, overexpression of b2M could promote the growth of SKOV3 cells in vitro, by colony formation and anchorage-independent growth assay, at least partially through the activation of PI3K/Akt pathway. Thus, b2M could be a potential therapeutic target in ovarian cancer.

摘要

卵巢癌是最致命的妇科癌症之一。基于抗体的治疗方法已成为越来越多恶性肿瘤的重要治疗方法。在这里,我们制备了一种针对 SKOV3 卵巢癌细胞的抗体池,该抗体池能够以剂量和时间依赖的方式诱导 SKOV3 细胞凋亡。通过 SEREX 分析,β2-微球蛋白(b2M)被鉴定为功能抗体的潜在靶分子。抗体池的免疫 IgG(i-IgG)对其他类型的癌细胞几乎没有影响,这可能是因为 SKOV3 细胞分泌更多的 b2M。进一步的研究表明,b2M 的特异性抗体确实也可以抑制 SKOV3 的生长。此外,b2M 的过表达可以通过集落形成和非锚定依赖性生长测定体外促进 SKOV3 细胞的生长,至少部分通过激活 PI3K/Akt 通路。因此,b2M 可能是卵巢癌的一个潜在治疗靶点。

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