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Updated: Jul 8, 2026
In Vitro Establishment of a Genetically Engineered Murine Head and Neck Cancer Cell Line using an Adeno-Associated Virus-Cas9 System
Published on: January 9, 2020
Adenovirus-expressed human hyperplasia suppressor gene induces apoptosis in cancer cells
Lina Wu1, Zhixin Li, Yingmei Zhang
1Center for Human Disease Genomics, Health Science Center, Peking University, 38 Xue-yuan Road, Beijing, 100083, P.R. China.
Abstract:
Hyperplasia suppressor gene (HSG), also called human mitofusin 2, is a novel gene that markedly suppresses the cell proliferation of hyperproliferative vascular smooth muscle cells from spontaneously hypertensive rat arteries. This gene encodes a mitochondrial membrane protein that participates in mitochondrial fusion and contributes to the maintenance and operation of the mitochondrial network. In this report, we showed that an adenovirus vector encoding human HSG (Ad5-hHSG) had an antitumor activity in a wide range of cancer cell lines. We further focused on the lung cancer cell line A549 and the colon cancer cell line HT-29 and then observed that Ad5-hHSG induced apoptosis both in vitro and in vivo. Confocal laser scanning microscopy and electron microscopy revealed that cells infected with Ad5-hHSG formed dose-dependent perinuclear clusters of fused mitochondria. Adenovirus-mediated hHSG overexpression induced apoptosis, cell cycle arrest, mitochondrial membrane potential (DeltaPsim) reduction and release of cytochrome c, caspase-3 activation, and cleavage of PARP in vitro. Overexpression of hHSG also significantly suppressed the growth of subcutaneous tumors in nude mice both ex vivo and in vivo. In addition, Ad5-hHSG increased the sensitivity of these cell lines to two chemotherapeutic agents, VP16 and CHX, and radiation. These results suggest that Ad5-hHSG may serve as an effective therapeutic drug against tumors.
Insights
Human mitofusin 2 (HSG) delivered via adenovirus (Ad5-hHSG) suppressed cancer cell proliferation and tumor growth. Ad5-hHSG induced apoptosis and enhanced sensitivity to chemotherapy and radiation, suggesting its therapeutic potential.
Area of Science:
- Molecular biology
- Cell biology
- Oncology
Background:
- Hyperplasia suppressor gene (HSG), also known as human mitofusin 2, regulates mitochondrial dynamics.
- Mitochondrial dysfunction is implicated in cancer development and progression.
Purpose of the Study:
- To investigate the antitumor activity of an adenovirus vector encoding human HSG (Ad5-hHSG).
- To evaluate the potential of Ad5-hHSG as a cancer therapeutic agent.
Main Methods:
- Adenovirus-mediated gene delivery of human HSG (Ad5-hHSG) into cancer cell lines (A549, HT-29) and tumor models.
- Assessment of apoptosis, cell cycle, mitochondrial membrane potential, and protein cleavage.
- In vitro and in vivo tumor growth inhibition assays.
- Evaluation of chemosensitization and radiosensitization.
Main Results:
- Ad5-hHSG demonstrated antitumor activity across various cancer cell lines.
- Infection with Ad5-hHSG induced apoptosis, cell cycle arrest, and mitochondrial abnormalities (fused mitochondria clusters).
- Overexpression of hHSG led to reduced mitochondrial membrane potential, cytochrome c release, caspase-3 activation, and PARP cleavage.
- Ad5-hHSG significantly suppressed tumor growth in vivo and enhanced sensitivity to VP16, CHX, and radiation.
Conclusions:
- Adenovirus-mediated human HSG overexpression exhibits potent antitumor effects.
- Ad5-hHSG induces cancer cell apoptosis and inhibits tumor growth through mitochondrial-related pathways.
- Ad5-hHSG represents a promising candidate for cancer therapy, potentially enhancing existing treatments.
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