Expression of CD40 and growth-inhibitory activity of CD40 agonist in ovarian carcinoma cells
Expression of CD40 and growth-inhibitory activity of CD40 agonist in ovarian carcinoma cells
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DOI：
10.1007/s00262-011-1194-0
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发表时间：
2012-03
期刊：
影响因子：
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通讯作者：
Yan Zhou;Jing He;L. Gou;Bo Mu;Wei-chan Liao;Cong Ma;Ping Tang;Shijie Zhou;Yong-jun Zhou;Jin-liang Yang
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文献类型：
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作者：
Yan Zhou;Jing He;L. Gou;Bo Mu;Wei-chan Liao;Cong Ma;Ping Tang;Shijie Zhou;Yong-jun Zhou;Jin-liang Yang
CD40受体是肿瘤坏死因子受体家族的成员，广泛表达于多种细胞类型。 CD40 激动剂抗体的抗肿瘤活性已在 B 细胞源性恶性肿瘤中观察到，但其对卵巢癌的活性仍不清楚。然而，在本文中，我们首次证实抗CD40激动剂抗体可以抑制卵巢癌细胞的生长并诱导细胞凋亡。本研究探讨了卵巢癌组织和细胞系中CD40的表达，同时评估了重组可溶性人CD40L（rshCD40L）和抗CD40激动剂抗体对细胞生长和凋亡的影响。流式细胞术和免疫组化检测表明CD40在卵巢癌细胞系和腹水来源的原发性卵巢癌细胞以及卵巢癌组织中表达。采用MTT法检测rshCD40L和抗CD40激动抗体对卵巢癌细胞的生长抑制作用，并采用流式细胞术和Hoechst染色分析凋亡肿瘤细胞的比例。我们的研究表明，CD40 在所有卵巢癌细胞系中表达，并在 86.2% (162/188) 的卵巢癌组织样本中进行检测，但在正常卵巢组织中不表达 (n=20)。用rshCD40L或抗CD40激动剂抗体治疗显着抑制卵巢癌细胞生长并诱导细胞凋亡。这些结果表明CD40在卵巢癌细胞上表达，而且rshCD40L和抗CD40激动抗体具有抑制人卵巢癌生长的治疗潜力。
The CD40 receptor is a member of the tumour necrosis factor receptor family and is widely expressed on various cell types. The antitumour activity of CD40 agonist antibody has been observed in B-cell-derived malignancies, but its activity on ovarian cancer remains unclear. However, in this paper, we first confirmed that the anti-CD40 agonist antibody could inhibit the growth of ovarian cancer cells and induce apoptosis. This study investigated the expression of CD40 by ovarian carcinoma tissues and cell lines, at the same time, we evaluated the effect of a recombinant soluble human CD40L (rshCD40L) and an anti-CD40 agonist antibody on cell growth and apoptosis. Flow cytometry and immunohistochemistry assay demonstrated that CD40 was expressed on ovarian carcinoma cell lines and primary ovarian carcinoma cells derived from ascites, as well as on ovarian carcinoma tissues. The growth inhibition of rshCD40L and the anti-CD40 agonist antibody on ovarian carcinoma cells was examined by MTT assay, and the proportion of apoptotic tumour cells was analysed by flow cytometry and Hoechst staining. Our study showed that CD40 was expressed on all ovarian carcinoma cell lines and was examined in 86.2% (162/188) of ovarian cancer tissue samples, but not in normal ovarian tissues (n= 20). Treatment with rshCD40L or anti-CD40 agonist antibody significantly inhibited ovarian carcinoma cell growth and induced apoptosis. Theses results suggest that CD40 is expressed on ovarian carcinoma cells, moreover, that rshCD40L and anti-CD40 agonist antibody have therapeutic potential to inhibit human ovarian cancer growth.