Children's Cancer Institute Australia, Lowy Cancer Research Centre, UNSW, Randwick, New South Wales 2031, Australia.
Br J Cancer. 2013 Jun 25;108(12):2485-94. doi: 10.1038/bjc.2013.205. Epub 2013 May 21.
The use of β-blockers for the management of hypertension has been recently associated with significant clinical benefits in cancer patients. Herein, we investigated whether β-blockers could be used in combination with chemotherapy for the treatment of neuroblastoma.
Seven β-blockers were tested for their antiproliferative and anti-angiogenic properties alone, and in combination with chemotherapy in vitro; the most potent drug combinations were evaluated in vivo in the TH-MYCN mouse model of neuroblastoma.
Three β-blockers (i.e., carvedilol, nebivolol and propranolol) exhibited potent anticancer properties in vitro and interacted synergistically with vincristine, independently of P-glycoprotein expression. β-blockers potentiated the anti-angiogenic, antimitochondrial, antimitotic and ultimately pro-apoptotic effects of vincristine. In vivo, β-blockers alone transiently slowed tumour growth as compared with vehicle only (P<0.01). More importantly, when used in combination, β-blockers significantly increased the tumour regression induced by vincristine (P<0.05). This effect was associated with an increase in tumour angiogenesis inhibition (P<0.001) and ultimately resulted in a four-fold increase in median survival, as compared with vincristine alone (P<0.01).
β-blockers can increase treatment efficacy against neuroblastoma, and their combination with chemotherapy may prove beneficial for the treatment of this disease and other drug-refractory cancers.
β受体阻滞剂在高血压治疗中的应用最近与癌症患者的显著临床获益相关。在此，我们研究了β受体阻滞剂是否可以与化疗联合用于神经母细胞瘤的治疗。
我们测试了 7 种β受体阻滞剂单独使用和与化疗联合使用的抗增殖和抗血管生成特性；在神经母细胞瘤 TH-MYCN 小鼠模型中，评估了最有效的药物组合的体内疗效。
三种β受体阻滞剂（即卡维地洛、比索洛尔和普萘洛尔）在体外表现出强大的抗癌特性，并与长春新碱协同作用，与 P 糖蛋白表达无关。β受体阻滞剂增强了长春新碱的抗血管生成、抗线粒体、抗有丝分裂和最终的促凋亡作用。在体内，β受体阻滞剂单独使用时与仅用载体相比，肿瘤生长暂时减缓（P<0.01）。更重要的是，当联合使用时，β受体阻滞剂显著增加了长春新碱诱导的肿瘤消退（P<0.05）。这种效果与肿瘤血管生成抑制的增加（P<0.001）有关，最终导致中位生存期比单独使用长春新碱增加了四倍（P<0.01）。
β受体阻滞剂可以提高神经母细胞瘤的治疗效果，其与化疗的联合应用可能对这种疾病和其他耐药性癌症的治疗有益。
