Department of Pathology, Anhui Medical University, 69# Meishan Road, Hefei, Anhui, 230032, PR China.
J Exp Clin Cancer Res. 2010 Mar 10;29(1):23. doi: 10.1186/1756-9966-29-23.
Anti-HER-2 antibodies targeting distinct epitopes have different biological functions on cancer cells. In a previous study, we demonstrated that anti-HER-2 engineering antibody ChA21 was able to bind to subdomain I of HER-2 extracellular domain. In this study, The effects of ChA21 on growth and apoptosis against ovarian carcinoma cell SK-OV-3 over-expressing HER-2 in vitro and in vivo were investigated.
Cell growth inhibition was evaluated by MTT assay. Apoptosis was detected by TUNEL stain, transmission electron microscopy and flow cytometry on cultured cells and tissue sections from nude mice xenografts. The apoptosis-related proteins Bax and Bcl-2 were assessed by immunohistochemistry.
We found that treatment of ChA21 caused a dose-dependent decrease of cell proliferation in vitro and a significant inhibition of tumor growth in vivo. ChA21 therapy led to a significant increase in the induction of apoptosis, and up-regulated the expression of Bax, while the expression of Bcl-2 was down-regulated.
These data suggest that ChA21 inhibits the growth and induces apoptosis of SK-OV-3 via regulating the balance between Bax and Bcl-2.
针对不同表位的抗 HER-2 抗体在癌细胞上具有不同的生物学功能。在之前的研究中，我们证明了抗 HER-2 工程抗体 ChA21 能够与 HER-2 细胞外结构域的亚结构域 I 结合。本研究旨在研究 ChA21 对体外和体内过度表达 HER-2 的卵巢癌细胞 SK-OV-3 的生长和凋亡的影响。
通过 MTT 测定评估细胞生长抑制。通过 TUNEL 染色、透射电镜和流式细胞术检测培养细胞和裸鼠异种移植组织切片中的细胞凋亡。通过免疫组化评估凋亡相关蛋白 Bax 和 Bcl-2。
我们发现 ChA21 处理导致体外细胞增殖呈剂量依赖性下降，体内肿瘤生长显著抑制。ChA21 治疗导致凋亡诱导显著增加，并上调 Bax 的表达，同时下调 Bcl-2 的表达。
这些数据表明，ChA21 通过调节 Bax 和 Bcl-2 之间的平衡抑制 SK-OV-3 的生长并诱导其凋亡。
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