COX-2 Selective Inhibitor as a Chemoprevention Drug in Oral Potentially Malignant Disorder
Date Issued
2010
Date
2010
Author(s)
Lin, Han-Wei
Abstract
In Taiwan, especially due to the habit of betel quid chewing, the annual incidence of oral cancer is more than 4,000 cases. This disease combines with severe morbidity, which results in the 5-year survival rate is about 55% only. Oral cancer is frequently preceded by multifocal oral potentially malignant disorders (PMD) during multistep carcinogenesis, but there is still no better approach proved to be able to attenuate the occurring of oral cancer by the turnover of oral PMD.
Cyclooxygenase-2 (COX-2) is induced by many factors including inflammatory stimuli, growth factors, tumor promoters, oncogenes, and carcinogens. Overexpression of COX-2, therefore, will inhibit many reactions like apoptosis, and increase cell proliferation, promote angiogenesis, or suppress immune surveillance, thus encourages the accumulation of genetic damage in epithelial cells. Previous in vitro and in vivo studies showed that COX-2 is overexpressed in oral PMD and head and neck squamous cell carcinoma, those results led us to hypothesize that inhibiting COX-2 in premalignant tissue would be an effective chemopreventive strategy for patients with oral PMD. In order to investigate the hypothesis, we go on this study.
In our study, 26 participants were recruited to give celecoxib, 400mg twice daily, for 12weeks. Biopsies were applied at baseline day and week 12. All participants enrolled in the study were required to have at least one pathologically proved oral PMD (hyperkeratosis, mild dysplasia and moderate dysplasia). After that, we evaluated the efficacy, safety and influences of celecoxib in patients with oral PMD. We also compared the effect of oral habits (betel quid chewing, cigarette smoking and alcohol drinking) with the efficacy of chemoprevention.
After 12-week chemoprevention, there were no significant differences in many characters including the size, the thickness, the color and the texture of the lesions, and there were also no obvious changes in pathological diagnosis. But we found COX-2 expression was significantly decreased and Ki-67 expression was positively correlated with COX-2 expression, however, there was no correlation in the expression of Survivin and Bcl-2 compared with COX-2. We also found that cigarette smoking, alcohol drinking and betel quid chewing were impacts for inhibition of COX-2 expression. In the periods of this study, participants had no cardiovascular side effects or serious illness situation. After the second biopsy, participants whose lesions still existed continued to have further treatments (cryotherapy, photodynamic therapy or surgical excision) and to be follow up so far（about 2 years）, more than half of those participants’ diseases were completely healed without recurrence.
Three-month chemoprevention regimen for the remission or reduction of the oral precancerous lesion was ineffective. However, keeping follow-up the original lesion still had the considerable research value. COX-2 might affect cell proliferation, but the impact of the pathway of apoptosis by taking celecoxib still need to be confirmed. In addition, bad oral habits will indeed affect COX-2 inhibition and therefore, while most of the participants continued to have those habits, we couldn’t easily judge the efficacy of COX-2 chemoprevention. Our results showed that COX-2 chemoprevention should possess its own value, but it is necessary to have more rigorous studies to investigate the role and value of COX-2 chemoprevention.
Subjects
Oral cancer
Oral potentially malignant disorder
Chemoprevention
celecoxib (CELEBREX?)
COX-2 inhibitor
SDGs
Type
thesis
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