Dipartimento di Scienze Farmaceutiche, Università di Salerno, Fisciano (Salerno), Italy.
Oncol Rep. 2010 Jan;23(1):171-5.
Rimonabant (SR141716), a highly selective cannabinoid receptor antagonist, exerts along with its anti-obesity action, pleiotropic functions affecting a broad range of diseases, from obesity-related co-morbidities to drug dependence and cancer. Several studies suggested an anti-tumour activity of rimonabant in several in vitro and in vivo models. In this study, we compared the anti-proliferative effect of SR141716 in the human colon cancer cell line DLD-1 with oxaliplatin, one of the cytotoxic drugs currently used in the treatment of colorectal cancer. We show that SR141716 inhibits DLD-1 cell proliferation similarly to oxaliplatin and if administered in combination SR141716 potentiated the inhibitory effect caused by oxaliplatin. Assessment of drug interaction was performed calculating combination index that showed a strong synergistic effect between the two drugs added to cells in combination. Our findings suggest that the combined synergic effect of SR141716 and oxaliplatin improves the blocking of colon cancer cell proliferation. Therefore, this combination merits further explorations in preclinical and clinical settings.
利莫那班（SR141716）是一种高选择性的大麻素受体拮抗剂，除了具有抗肥胖作用外，还具有多种影响广泛疾病的多效性功能，从肥胖相关的合并症到药物依赖和癌症。几项研究表明，利莫那班在几种体外和体内模型中具有抗肿瘤活性。在这项研究中，我们比较了 SR141716 在人结肠癌细胞系 DLD-1 中的抗增殖作用与奥沙利铂（目前用于治疗结直肠癌的细胞毒性药物之一）的作用。我们发现 SR141716 抑制 DLD-1 细胞增殖的效果与奥沙利铂相似，如果联合使用，SR141716 可增强奥沙利铂引起的抑制作用。通过计算组合指数评估药物相互作用，该指数显示两种药物联合添加到细胞中时具有很强的协同作用。我们的研究结果表明，SR141716 和奥沙利铂的联合协同作用可改善结肠癌细胞增殖的阻断。因此，这种联合值得在临床前和临床环境中进一步探索。
