Anti-tumor effects of propranolol: Adjuvant activity on a transplanted murine breast cancer model

Anti-tumor effects of propranolol: Adjuvant activity on a transplanted murine breast cancer model
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DOI:
10.1016/j.biopha.2018.05.002
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发表时间:
2018-08-01
影响因子:
7.5
通讯作者:
Mahdavi, Mehdi
Mahdavi, Mehdi
中科院分区:
医学2区
文献类型:
--
作者:
Ashrafi, Somayeh;Shapouri, Reza;Mahdavi, Mehdi

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心得安(Propranolol, Pro)是一种非特异性β -肾上腺素能阻断药物,竞争性地阻止儿茶酚胺与受体的结合,抑制癌细胞。心得安的抗肿瘤作用已在不同类型的肿瘤中得到证实。在本研究中,我们评估了心得安联合肿瘤疫苗模型对乳腺荷瘤小鼠免疫参数的佐剂活性。将乳腺肿瘤块植入近交系BALB/C雌性小鼠的侧腹。荷瘤小鼠用肿瘤抗原裂解物疫苗与心得安/疫苗(Pro/Vac)联合治疗(治疗组),心得安与PBS(对照组)连续治疗5 d,每12 h注射1次,试验组注射3次,间隔1周。免疫疗程结束后,取荷瘤小鼠脾脏,体外刺激细胞悬液,用ELISA试剂盒检测脾细胞上清中细胞因子水平。与疫苗组相比,肿瘤裂解液联合普萘洛尔免疫可显著增加IL-2、IL-4、IL-12、IL-17和ifn - γ细胞因子。考虑到抑制肿瘤生长,心得安似乎是一种有效的免疫调节剂,能够诱导细胞免疫反应对抗乳腺癌。
Propranolol (Pro), a non-specific beta-adrenergic blocking drug, competitively prevents the binding of catecholamines to receptors and suppresses cancer cells. The anti-tumor activity of propranolol has been proved in different kinds of cancers. In this study, we assessed the adjuvant activity of propranolol combined with a tumor vaccine model on the immunological parameters of breast tumor-bearing mice. Breast tumor pieces were implanted into the flank of inbred BALB/C female mice from stock mice. Tumor-bearing mice were treated with tumor antigen lysate vaccine and propranolol/Vaccine (Pro/Vac) combination (as treatment groups), propranolol and PBS (as control groups) for 5 consecutive days, every 12 h. Moreover, all experimental groups received vaccine for three times with one-week interval via s.c injection. After immunization courses, spleens of tumor-bearing mice were removed and dissected, cell suspension was stimulated in vitro, and the cytokine levels in supernatant of splenocytes were measured via commercial ELISA kits. Compared with the vaccine group, immunization with tumor lysate in combination with propranolol significantly increased IL-2, IL-4, IL-12, IL-17, and IFN-gamma cytokines. Considering the suppression of tumor growth, propranolol seems to be a potent immunomodulator capable of inducing cellular immune responses against breast cancer.