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Published on: February 9, 2024
WW domain containing oxidoreductase induces apoptosis in gallbladder-derived malignant cell by upregulating
Dong Wei1, Xiaowen Zhang, Hao Zou
1Department of Hepatopancreatobiliary Surgery, The Second Affiliated Hospital of Kunming Medical University, Kunming, 650101, Yunnan, People's Republic of China.
Abstract:
Gallbladder cancer (GBC) is one leading cause of cancer-related death worldwide. WW domain-containing oxidoreductase (WWOX) is a tumor suppressor gene which can suppress proliferation of a variety of tumors. However, little was known about the relationships between WWOX and gallbladder cancer. In the current study, we intended to investigate the tumor suppressive role of WWOX in gallbladder malignant cells both in vitro and in vivo, and explore the potential mechanism of tumor toxic function of WWOX. Our results have shown that WWOX triggerred apoptosis in GBC cells and increased the expression of P73 and PUMA in cytoplasm. We also have found that Bax has been upregulated after overexpression of WWOX, whereas, Bcl-2 was downregulated by WWOX. To further validate the results in vivo, we evaluated the tumor suppressive role of WWOX in mouse model of gallbladder cancer. The results have shown that the proliferation of the tumor was inhibited after delivery of WWOX, and the expressions of P73 and PUMA were upregulated in target tissues. The mice models administrated with WWOX have shown better prognosis than mice in negative control groups. The results from our study indicated that WWOX could be used as a therapeutic agent in the gene therapy of gallbladder cancer.
Insights
WW domain-containing oxidoreductase (WWOX) suppresses gallbladder cancer by inducing apoptosis and inhibiting tumor growth. This study suggests WWOX holds potential as a therapeutic agent for gallbladder cancer gene therapy.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Genetics
Background:
- Gallbladder cancer (GBC) is a significant cause of cancer mortality globally.
- The tumor suppressor gene WW domain-containing oxidoreductase (WWOX) is known to inhibit various tumor types.
- The specific role of WWOX in gallbladder cancer remains largely unexplored.
Purpose of the Study:
- To investigate the tumor-suppressive function of WWOX in gallbladder cancer cells.
- To elucidate the underlying molecular mechanisms of WWOX's anti-cancer activity.
- To evaluate the therapeutic potential of WWOX in gallbladder cancer models.
Main Methods:
- In vitro studies involving gallbladder cancer cell lines.
- In vivo experiments using a mouse model of gallbladder cancer.
- Analysis of apoptosis-related gene expression (P73, PUMA, Bax, Bcl-2).
- Assessment of tumor proliferation and prognosis in mouse models.
Main Results:
- WWOX overexpression induced apoptosis in gallbladder cancer cells.
- WWOX modulated the expression of key apoptosis regulators: P73, PUMA, Bax, and Bcl-2.
- In vivo delivery of WWOX inhibited tumor proliferation and improved prognosis in mice.
- Upregulation of P73 and PUMA was observed in target tissues following WWOX administration.
Conclusions:
- WWOX exhibits significant tumor-suppressive effects in gallbladder cancer.
- WWOX exerts its function by promoting apoptosis and regulating key molecular pathways.
- WWOX demonstrates potential as a novel therapeutic agent for gene therapy in gallbladder cancer.
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