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Quantifying Antibody-Dependent Cellular Cytotoxicity in a Tumor Spheroid Model: Application for Drug Discovery
Published on: April 26, 2024
Anti-HER-2 engineering antibody ChA21 inhibits growth and induces apoptosis of SK-OV-3 cells
Anli Zhang1, Hua Xue, Xiaoguang Ling
1Department of Pathology, Anhui Medical University, 69# Meishan Road, Hefei, Anhui, 230032, PR China.
Background And Aims:
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.
Methods:
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.
Results:
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.
Conclusion:
These data suggest that ChA21 inhibits the growth and induces apoptosis of SK-OV-3 via regulating the balance between Bax and Bcl-2.
Insights
The anti-HER-2 antibody ChA21 effectively inhibits ovarian cancer cell growth and promotes apoptosis. This therapeutic effect is achieved by modulating the expression of key apoptosis-regulating proteins, Bax and Bcl-2.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Anti-HER-2 antibodies exhibit diverse biological functions based on their targeted epitopes.
- The engineered antibody ChA21 binds to subdomain I of the HER-2 extracellular domain.
- Ovarian carcinoma cell line SK-OV-3 overexpresses HER-2.
Purpose of the Study:
- To investigate the effects of ChA21 on the growth and apoptosis of HER-2-overexpressing SK-OV-3 cells.
- To evaluate the in vitro and in vivo efficacy of ChA21.
- To elucidate the molecular mechanisms underlying ChA21's anti-cancer activity.
Main Methods:
- Cell proliferation assessed using MTT assay.
- Apoptosis detected via TUNEL staining, transmission electron microscopy, and flow cytometry.
- Expression of apoptosis-related proteins Bax and Bcl-2 analyzed by immunohistochemistry.
Main Results:
- ChA21 treatment resulted in dose-dependent inhibition of cell proliferation in vitro.
- Significant tumor growth inhibition observed in vivo following ChA21 therapy.
- ChA21 therapy increased apoptosis induction and upregulated Bax expression while downregulating Bcl-2 expression.
Conclusions:
- ChA21 demonstrates significant anti-proliferative and pro-apoptotic effects on SK-OV-3 cells.
- The mechanism involves regulating the balance between Bax and Bcl-2 protein expression.
- ChA21 holds potential as a therapeutic agent for HER-2-positive ovarian cancer.
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