A Novel Small Molecular Antibody, HER2-Nanobody, Inhibits Tumor Proliferation in HER2-Positive Breast Cancer Cells In Vitro and In Vivo.

A Novel Small Molecular Antibody, HER2-Nanobody, Inhibits Tumor Proliferation in HER2-Positive Breast Cancer Cells In Vitro and In Vivo.
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一种新型的小分子抗体HER2-纳米病,在体外和体内抑制HER2阳性乳腺癌细胞中的肿瘤增殖。

DOI:
10.3389/fonc.2021.669393
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发表时间:
2021
影响因子:
4.7
通讯作者:
Ding K
Ding K
中科院分区:
医学3区
文献类型:
--
作者:
Yan Y;Cheng X;Li L;Zhang R;Zhu Y;Wu Z;Ding K

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乳腺癌是世界范围内,特别是发展中国家妇女最常见的恶性肿瘤。赫赛汀是一种单克隆抗体,对HER 2阳性乳腺癌具有抗肿瘤作用。然而,赫赛汀的大分子量限制了其应用。在本研究中,我们构建并筛选了HER 2-纳米抗体,并验证了其在HER 2阳性乳腺癌细胞中的肿瘤抑制作用。构建、筛选、纯化HER 2-纳米抗体,并在体外证明其抑制HER 2阳性乳腺癌细胞的细胞总数、活力、集落形成和有丝分裂,并促进细胞凋亡。用HER 2-纳米抗体处理,肿瘤生长通过体内瘤内注射和尾静脉内注射均被显著抑制。HER 2-nanobody抑制HER 2阳性乳腺癌细胞中ERK和AKT的磷酸化。RAS-RAF-MAPK和PI 3 K-AKT-mTOR是HER 2的两条重要通路。HER 2-nanobody可能通过抑制ERK和AKT的磷酸化而发挥抑瘤作用。因此,HER 2-纳米抗体可用作抑制HER 2阳性乳腺癌的小分子抗体。
Breast cancer is the most common malignant cancer in women worldwide, especially in developing countries. Herceptin is a monoclonal antibody with an antitumor effect in HER2-positive breast cancer. However, the large molecular weight of Herceptin limited its employment. In this study, we constructed and screened HER2-nanobody and verified its tumor-suppressive effect in HER2-positive breast cancer cells. HER2-nanobody was established, filtrated, purified, and was demonstrated to inhibit cell total number, viability, colony formation and mitosis, and promote cell apoptosis in HER2-positive breast cancer cells in vitro. Treated with HER2-nanobody, tumor growth was significantly inhibited by both intratumor injection and tail intravenous injection in vivo. The phosphorylation of ERK and AKT was restrained by HER2-nanobody in HER2-positive breast cancer cells. RAS-RAF-MAPK and PI3K-AKT-mTOR are two important pathways involved in HER2. It was credible for HER2-nanobody to play the tumor suppressive role by inhibiting the phosphorylation of ERK and AKT. Therefore, HER2-nanobody could be employed as a small molecular antibody to suppress HER2-positive breast cancer.
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