A Novel Small Molecular Antibody, HER2-Nanobody, Inhibits Tumor Proliferation in HER2-Positive Breast Cancer Cells In Vitro and In Vivo
Open Access
- 12 May 2021
- journal article
- research article
- Published by Frontiers Media SA in Frontiers in Oncology
Abstract
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.This publication has 60 references indexed in Scilit:
- Nanobodies: Natural Single-Domain AntibodiesAnnual Review of Biochemistry, 2013
- Pertuzumab plus Trastuzumab plus Docetaxel for Metastatic Breast CancerThe New England Journal of Medicine, 2012
- Four-Year Follow-Up of Trastuzumab Plus Adjuvant Chemotherapy for Operable Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer: Joint Analysis of Data From NCCTG N9831 and NSABP B-31Journal of Clinical Oncology, 2011
- CXCR4 nanobodies (VHH-based single variable domains) potently inhibit chemotaxis and HIV-1 replication and mobilize stem cellsProceedings of the National Academy of Sciences of the United States of America, 2010
- Novel anticancer targets: revisiting ERBB2 and discovering ERBB3Nature Reviews Cancer, 2009
- Autocrine Human Growth Hormone Stimulates Oncogenicity of Endometrial Carcinoma CellsEndocrinology, 2008
- Trastuzumab after Adjuvant Chemotherapy in HER2-Positive Breast CancerThe New England Journal of Medicine, 2005
- β-Lactamase Inhibitors Derived from Single-Domain Antibody Fragments Elicited in the CamelidaeAntimicrobial Agents and Chemotherapy, 2001
- Effects of oncogenic ErbB2 on G1 cell cycle regulators in breast tumour cellsOncogene, 2000
- Human Breast Cancer: Correlation of Relapse and Survival with Amplification of the HER-2/ neu OncogeneScience, 1987