Use of Non-steroidal Anti-inflammatory Drugs for Chemoprevention of Inflammation-induced Prostate Cancer

Turkish Journal of Pharmaceutical Sciences

article

Bilge DEBELEÇ BÜTÜNER¹  Mert Burak ÖZTÜRK² 

[1] Ege University, Faculty of Pharmacy, Department of Pharmaceutical Biotechnology;Ege University, Faculty of Engineering, Department of Bioengineering, Cancer Biology Laboratory

关键词: NSAID;    prostate cancer;    inflammation;    androgen receptor;    NKX3.1;   

DOI  :  10.4274/tjps.41636

来源: Galenos Yayinevi

【 摘 要 】

Objectives: Chronic inflammation has been known as one of the major causes of cancer progression and 25% of cancer cases initiate due to chronic inflammation according to epidemiologic data. It has been determined that chronic inflammation induces carcinogenesis through the abrogation of cell proliferation, apoptosis, and angiogenesis mechanisms. Therefore, it is believed that inhibition of inflammation-induced carcinogenic mechanisms is an efficient therapeutic strategy in drug development studies of cancer chemoprevention. It has also been observed that use of anti-inflammatory drugs reduces the incidence of cancer, and the risk of developing prostate cancer decreases 15-20% with regular use of aspirin and non-steroidal anti-inflammatory drugs (NSAID). Materials and Methods: In this study, we investigated the effects of some clinically used NSAIDs on cellular mechanisms that play a role in inflammation-induced prostate carcinogenesis. Inhibition activities on the nuclear factor kappa-B signaling pathway, which activates tumorigenic mechanisms, as well as alterations on androgen receptor signaling, which regulates the proliferation of prostate cells, were investigated. In addition, protein kinase B (Akt) activation, which is stimulated a the inflammatory microenvironment, was examined. Results: The results showed that anti-inflammatory agents alter the protein levels of androgen receptors as well as tumor suppressor NKX3.1, and might trigger an unexpected increase in Akt(S473) level, which induces tumorigenesis. Conclusion: It is suggested that inflammatory pathways and prostate carcinogenesis-specific mechanisms should be taken into account for the use of anti-inflammatory drugs for chemoprevention of inflammation-induced prostate cancer.

【 授权许可】

Unknown