Department of Oral Pathology, Federal University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul.
Department of Oral Diagnosis, University of Campinas, Piracicaba, São Paulo.
Eur J Cancer Prev. 2021 Jul 1;30(4):315-321. doi: 10.1097/CEJ.0000000000000626.
The multistep process of oral carcinogenesis provides a biological rationale for the use of chemoprevention in individuals at increased risk of developing oral cancer. We aimed to determine if low doses of propranolol can prevent the development of oral cancer using a tobacco-relevant and p53-associated animal model of cancer initiation. Twenty-six Wistar rats were randomly allocated into two groups, vehicle, and propranolol. All animals received 4-nitroquinoline N-oxide (4NQO) at 25 ppm diluted in the drinking water for 20 weeks. Animals from the propranolol group received propranolol (0.1 mg/kg) 5 days per week by gavage for 18 weeks. The clinical analysis was performed by measuring the area of the lesion and assessment of scores based on lesion appearance (papule; plaque; nodule or ulcerated). Histopathological analysis was performed to determine the presence of epithelial dysplasia or invasive squamous cell carcinoma (SCC). The average lesion area in 4NQO + vehicle and in 4NQO + propranolol groups were 0.20 and 0.28 mm2, respectively (P = 0.53). The percentage of cases clinically graded as papules, thick plaques, nodular areas, and ulcerated lesions was similar between groups (P = 0.94). Histopathological diagnosis also did not differ between groups (P = 0.65), with 54.5 and 70% of cases being diagnosed as SCC in 4NQO and in 4NQO + propranolol groups, respectively. In conclusion, daily doses propranolol at 0.1 mg/kg were not as effective as a chemopreventive therapy in an animal model of 4NQO-induced carcinogenesis.
口腔癌变的多步骤过程为在罹患口腔癌风险增加的个体中使用化学预防提供了生物学依据。我们旨在通过烟草相关和 p53 相关的癌症起始动物模型来确定低剂量普萘洛尔是否可以预防口腔癌的发生。26 只 Wistar 大鼠被随机分为两组，即载体组和普萘洛尔组。所有动物均接受浓度为 25ppm 的 4-硝基喹啉 N-氧化物（4NQO）饮用水，为期 20 周。普萘洛尔组的动物每周 5 天通过灌胃给予普萘洛尔（0.1mg/kg），为期 18 周。通过测量病变面积和根据病变外观（丘疹；斑块；结节或溃疡性）进行评分来进行临床分析。进行组织病理学分析以确定是否存在上皮异型增生或侵袭性鳞状细胞癌（SCC）。在 4NQO+载体组和 4NQO+普萘洛尔组中，平均病变面积分别为 0.20 和 0.28mm2（P=0.53）。丘疹、厚斑块、结节区域和溃疡性病变的临床分级病例百分比在两组之间相似（P=0.94）。组织病理学诊断也无差异（P=0.65），在 4NQO 和 4NQO+普萘洛尔组中，分别有 54.5%和 70%的病例被诊断为 SCC。总之，每日剂量为 0.1mg/kg 的普萘洛尔在 4NQO 诱导的癌变动物模型中不如化学预防治疗有效。
