Murugan Sengottuvelan, Rousseau Bénédicte, Sarkar Dipak K
Endocrine Research Program, Department of Animal Sciences, Rutgers, The State University of New Jersey, 67 Poultry Farm Lane, New Brunswick, NJ 08901, USA.
Cancers (Basel). 2021 Sep 28;13(19):4858. doi: 10.3390/cancers13194858.
Cancer progression is known to be promoted by increased body stress caused by elevated beta-adrenergic and opioidergic nervous system activities. The effects of β2-adrenergic blocker propranolol (PRO) and μ-opioid receptor antagonist naltrexone (NTX) were tested using a preclinical model of human breast cancer. These drugs, individually, and more potently when combined, inhibited the cell growth and progression of breast cancer cells in vitro in cultures, and in vivo in rat xenografts. The antitumor activities of these drugs were associated with direct cell intrinsic effects, including increased cell growth arrest, elevated levels of apoptotic proteins, and reduced production of epithelial-mesenchymal transition factors by the tumor cells, as well as effects on innate immune activation and reduced inflammatory cytokine levels in plasma. These data suggest that the combined treatments of PRO and NTX produce impressive antitumor effects in the preclinical breast cancer model, and thereby may provide a new combinatorial treatment strategy with more clinical treatment modalities.
已知β-肾上腺素能和阿片样物质能神经系统活动增强所导致的身体应激增加会促进癌症进展。使用人乳腺癌临床前模型测试了β2-肾上腺素能阻滞剂普萘洛尔（PRO）和μ-阿片受体拮抗剂纳曲酮（NTX）的作用。这些药物单独使用时，联合使用时效果更强，在体外培养物中以及在大鼠异种移植瘤的体内均能抑制乳腺癌细胞的生长和进展。这些药物的抗肿瘤活性与直接的细胞内在效应有关，包括细胞生长停滞增加、凋亡蛋白水平升高、肿瘤细胞上皮-间质转化因子产生减少，以及对先天免疫激活的影响和血浆中炎症细胞因子水平降低。这些数据表明，PRO和NTX的联合治疗在临床前乳腺癌模型中产生了令人印象深刻的抗肿瘤作用，从而可能提供一种具有更多临床治疗方式的新联合治疗策略。
