Psychoneuroimmunology Laboratory, Psychosomatic Research Center, Oral Oncology Center, São Paulo State University (Unesp), School of Dentistry, 1193 José Bonifácio St, Araçatuba, São Paulo, 15050-015, Brazil.
Department of Diagnosis and Surgery, São Paulo State University (Unesp), School of Dentistry, 1193 José Bonifácio St, Araçatuba, São Paulo, 15050-015, Brazil.
Cancer Chemother Pharmacol. 2020 Nov;86(5):681-686. doi: 10.1007/s00280-020-04149-2. Epub 2020 Sep 27.
Beta-adrenergic signaling can influence cancer progression and the use of beta blockers as adjuvant drugs in oncologic patients has been suggested. However, the involvement of beta-adrenergic blockers in tumorigenesis is poorly understood. This study investigated the action of beta-adrenergic blocker propranolol on tumor onset using a preclinical model of chemically induced oral cancer.
Thirty-two male Wistar rats were subjected to daily subcutaneous injection of beta-blocker propranolol (10 mg/kg; SubQ), while another 32 rats received only a PBS injection (sham group). One week after starting propranolol treatment, all rats were submitted to chemical induction of oral carcinogenesis with 4-nitroquinoline-1-oxide (4NQO). After 16 weeks, they were assessed for occurrence of oral squamous cell carcinoma (OSCC), in addition to measurement of tumor volume and thickness, and tissue levels of cytokines IL-6, TNF-alpha and IL-10 in the tumor microenvironment.
Propranolol treatment reduced the occurrence of OSCC by 31%, 95% CI ( - 127, 216). Beta-adrenergic blocker significantly decreased thickness of OSCC when compared with PBS. Rats treated with propranolol exhibited a lower tumor volume when compared with control rats, but this result did not reach statistical significance. Tumors from propranolol-treated rats exhibited reduced concentrations of pro-inflammatory cytokines IL-6 and TNF-α. There was no difference in the IL-10 levels between tumors from propranolol- and sham-treated rats.
Beta-adrenergic signaling may be one of the mechanisms associated with chemically induced oral carcinogenesis.
β-肾上腺素能信号可以影响癌症的进展，并且已经有人建议将β-受体阻滞剂作为肿瘤患者的辅助药物。然而，β-肾上腺素能阻滞剂在肿瘤发生中的作用仍知之甚少。本研究使用化学诱导性口腔癌的临床前模型，研究了β-肾上腺素能阻滞剂普萘洛尔对肿瘤发生的作用。
32 只雄性 Wistar 大鼠每天接受β-受体阻滞剂普萘洛尔（10mg/kg；皮下注射），而另外 32 只大鼠仅接受 PBS 注射（假手术组）。普萘洛尔治疗开始后一周，所有大鼠均接受 4-硝基喹啉-1-氧化物（4NQO）化学诱导口腔致癌作用。16 周后，评估口腔鳞状细胞癌（OSCC）的发生情况，并测量肿瘤体积和厚度，以及肿瘤微环境中细胞因子 IL-6、TNF-α 和 IL-10 的组织水平。
普萘洛尔治疗使 OSCC 的发生率降低了 31%，95%可信区间（-127，216）。与 PBS 相比，β-肾上腺素能阻滞剂显著降低了 OSCC 的厚度。与对照组大鼠相比，接受普萘洛尔治疗的大鼠的肿瘤体积较小，但这一结果没有达到统计学意义。与接受安慰剂治疗的大鼠相比，接受普萘洛尔治疗的大鼠的肿瘤中促炎细胞因子 IL-6 和 TNF-α 的浓度降低。普萘洛尔和假手术治疗大鼠的肿瘤中 IL-10 水平没有差异。
β-肾上腺素能信号可能是与化学诱导性口腔癌发生相关的机制之一。
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