Adenovirus-delivered wwox inhibited lung cancer growth in vivo in a mouse model
1Department of Thoracic Surgery, The Affiliated Hospital of Jiangnan University and Wuxi Fourth People's Hospital, Wuxi, Jangsu, China.
Abstract:
Lung cancer is the most prevalent and deadly malignancy worldwide. This study investigated the possibility of inhibiting lung cancer in vivo with adenovirus-delivered WW domain-containing oxidoreductase (wwox). The lung cancer model was established by inoculating A549 lung cancer cells into the pleural space of nude mice. The control or wwox adenovirus was injected into the pleural space 7 days after cell inoculation and 14 days after first injection. The tumor number and burdens were measured 2 weeks after second virus injection. The carcinoembryonic antigen (CEA) and alpha-feto protein (AFP) levels in pleural effusion were analyzed by enzyme-linked immunosorbent assay. Apoptosis, proliferation and angiogenesis of tumor cells were assessed by terminal deoxinucleotidyl transferase-mediated dUTP-fluorescein nick end labeling assay, proliferating cell nuclear antigen (PCNA) and CD31 staining, respectively. Ectopic wwox significantly reduced both the number and size of lung tumors accompanied by substantially lower CEA and AFP levels in pleural effusion. The expression levels of Bcl2, Bcl-xL, vascular endothelial growth factor, PCNA-positive and CD31-positive cells in the tumors were significantly decreased, whereas levels of p21 and p73 and apoptotic cells markedly increased in mice receiving the wwox virus. These data demonstrated that wwox delivered by adenovirus was able to inhibit the growth of lung cancer in vivo, indicating the potential of using wwox as a gene therapy agent for lung cancer.
Insights
Gene therapy using adenovirus-delivered WW domain-containing oxidoreductase (wwox) significantly inhibited lung cancer growth in mice. This approach reduced tumor size and markers, offering a potential new treatment for lung cancer.
Area of Science:
- Oncology
- Gene Therapy
- Molecular Biology
Background:
- Lung cancer remains a leading cause of cancer-related mortality globally.
- Effective therapeutic strategies are urgently needed to combat this prevalent malignancy.
Purpose of the Study:
- To investigate the efficacy of adenovirus-delivered WW domain-containing oxidoreductase (wwox) in inhibiting lung cancer growth in vivo.
- To evaluate the impact of wwox gene therapy on tumor progression, apoptosis, proliferation, and angiogenesis in a mouse model.
Main Methods:
- A lung cancer model was established using A549 cells in nude mice.
- Adenovirus carrying wwox or a control was administered intratumorally.
- Tumor burden, serum tumor markers (CEA, AFP), apoptosis, proliferation (PCNA), and angiogenesis (CD31) were assessed.
Main Results:
- Intratumoral wwox delivery significantly reduced lung tumor number and size.
- CEA and AFP levels were substantially decreased in the pleural effusion of treated mice.
- wwox therapy increased apoptosis and p21/p73 expression while decreasing Bcl2, Bcl-xL, VEGF, PCNA, and CD31 expression.
Conclusions:
- Adenovirus-mediated delivery of wwox demonstrates potent inhibition of lung cancer growth in vivo.
- wwox acts by suppressing proliferation and angiogenesis and promoting apoptosis in lung tumors.
- wwox holds promise as a novel gene therapy agent for lung cancer treatment.
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