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INTERNATIONAL CONGRESS OF

CancerGenetics

• The Role of Cyclooxygenase-2 Expression in the Pathogenesis and Progression of Bladder Cancer

• Mohammadamir kakaee,^1,* Amirhossein yusefi,²
  1. Shahid Beheshti University of Medical Sciences
  2. Shahid Beheshti University of Medical Sciences
  
  
  
• Introduction: Bladder cancer is a significant global health burden, ranking as the ninth most common cancer worldwide. In 2020, there were approximately 573,000 new cases of bladder cancer and 213,000 deaths globally. The high incidence and mortality rates of bladder cancer underscore the need for effective therapeutic strategies to combat this disease.The enzyme cyclooxygenase-2 (COX-2) has been implicated in various cancers, including bladder cancer. Indeed, numerous studies have shown that COX-2 is not merely a bystander in the process of carcinogenesis, but rather actively participates in the development and progression of cancer. Furthermore, COX-2 has been linked to several key mechanisms that contribute to cancer malignancy, including the suppression of apoptosis, evasion of host immune surveillance, and promotion of angiogenesis.In light of these findings, targeting COX-2 may offer a promising approach to cancer therapy. Specifically, COX-2 inhibitors have been shown to exhibit anti-tumor activity by inhibiting the growth and spread of cancer cells, as well as by improving the response to chemotherapy and radiation. Given the importance of COX-2 in bladder cancer, an in-depth understanding of the mechanisms underlying its antitumor activity is crucial for the optimal application of COX-2 inhibitors in clinical practice
• Methods: A comprehensive literature search was conducted using three major databases: PubMed, Web of Science, and SID, covering publications from 1996 to 2024. The search focused on the key terms "bladder cancer" and "COX-2 expression."In the SID database, only one relevant study was identified. The PubMed search initially retrieved 200 articles. After applying the inclusion criteria, 13 articles were selected for detailed analysis. The search in Web of Science was also performed, and after the removal of duplicate studies, a total of 17 articles were reviewed in-depth.
• Results: Cyclooxygenase-2 (COX-2) is a critical enzyme responsible for converting arachidonic acid into prostaglandins, molecules that play a significant role in inflammation and cell growth. Typically, COX-2 is induced by various stimuli, including growth factors, cytokines, and bacterial lipopolysaccharides. Mechanism of COX-2 in Cancer Induction and Overexpression COX-2 is overexpressed in many cancers, including colorectal, breast, and gastric cancers. This overexpression often arises from inflammation and oncogenic pathways. It is crucial to understand this mechanism to develop effective treatments. Prostaglandin Production COX-2 catalyzes the production of prostaglandin E2 (PGE2), which plays a critical role in promoting tumor growth. PGE2 enhances angiogenesis, inhibits apoptosis, and stimulates cell proliferation. This process creates a positive feedback loop, where PGE2 induces COX-2 expression, sustaining high levels of both in the tumor microenvironment. Pathways and Effects Angiogenesis COX-2 promotes the formation of new blood vessels, which supplies tumors with the necessary nutrients and oxygen for growth and metastasis. Invasion and Metastasis COX-2 enhances the invasive capabilities of cancer cells by modulating the extracellular matrix and promoting epithelial-mesenchymal transition (EMT). This process enables cancer cells to migrate and invade surrounding tissues. Immune Suppression COX-2 can suppress the immune response against tumors, allowing them to evade detection and destruction. Understanding the role of COX-2 in immune suppression is crucial for developing immunotherapy strategies. In summary, COX-2 plays a central role in cancer progression through its involvement in inflammation, angiogenesis, and immune modulation. Its overexpression and the subsequent increase in prostaglandin production create a tumor-promoting environment that fuels cancer growth and metastasis.
• Conclusion: The cumulative evidence from multiple studies suggests that Cyclooxygenase-2 (COX-2) plays a multifaceted role in the development and progression of bladder cancer.Gee (2006) and Dhawan (2008) found that COX-2 inhibitors can impede bladder cancer cell growth, although the underlying mechanisms may not involve COX-2 activity. Shariat (2003) demonstrated a link between COX-2 expression and advanced disease stages, but its prognostic value is limited. Additionally, Badawi (2002) highlighted the influence of smoking on COX-2 expression, which may contribute to bladder cancer development. Recent studies have explored the feasibility of using targeted therapies, such as fluorocoxib A (Bourn, 2019), to monitor COX-2 expression changes and potentially enhance treatment outcomes. Zuo (2014) also provided evidence that ART can induce apoptosis through COX-2 downregulation, offering a promising novel therapeutic approach. Overall, these studies indicate that while COX-2 plays a significant role in bladder cancer, its inhibition may have both COX-2-dependent and -independent effects, and its expression is influenced by various factors, including smoking and targeted therapies.
• Keywords: Cox-2