Beta 2 Adrenergic Receptor Antagonist Propranolol and Opioidergic Receptor Antagonist Naltrexone Produce Synergistic Effects on Breast Cancer Growth Prevention by Acting on Cancer Cells and Immune Environment in a Preclinical Model of Breast Cancer.
Beta 2 Adrenergic Receptor Antagonist Propranolol and Opioidergic Receptor Antagonist Naltrexone Produce Synergistic Effects on Breast Cancer Growth Prevention by Acting on Cancer Cells and Immune Environment in a Preclinical Model of Breast Cancer.
复制标题
DOI：
10.3390/cancers13194858
复制
发表时间：
2021-09-28
期刊：
影响因子：
5.2
通讯作者：
Sarkar DK
中科院分区：
文献类型：
--
作者：
Murugan S;Rousseau B;Sarkar DK
在这里，我们发现普萘洛尔（一种用于治疗高血压的β受体阻滞剂）和纳曲酮（一种用于治疗药物和酒精依赖的阿片类拮抗剂）联合使用时，可以对肿瘤生长和肿瘤质量产生显着的抑制作用，同时提高存活率，增加NK细胞活性，并降低血浆中炎症细胞因子水平。这些抗肿瘤作用是由于减少肿瘤细胞增殖、诱导细胞凋亡以及防止肿瘤中上皮间质转化而产生的。我们的数据确定了一种在临床前乳腺癌模型中结合批准的各类药物的新型治疗方法。众所周知，β-肾上腺素能和阿片能神经系统活动升高引起的身体压力增加会促进癌症的进展。使用人类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。这些药物单独使用或联合使用时更有效地抑制体外培养物中乳腺癌细胞的生长和进展，以及体内大鼠异种移植物中的乳腺癌细胞的生长和进展。这些药物的抗肿瘤活性与直接细胞内在效应相关，包括增加细胞生长停滞、提高凋亡蛋白水平、减少肿瘤细胞产生上皮-间质转化因子，以及对先天免疫激活的影响和降低血浆中炎症细胞因子水平。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效果，从而可能提供一种具有更多临床治疗方式的新的组合治疗策略。
Here, we show that propranolol, a beta blocker used to treat high blood pressure, and naltrexone, an opiate antagonist used for drug and alcohol dependence, when combined, produce marked inhibitory effects on tumor growth and tumor mass while improving the survival rate, increasing NK cell activity, and reducing inflammatory cytokine levels in plasma. These antitumor effects resulted from a reduction in tumor cell proliferation, the induction of cellular apoptosis, and the prevention of epithelial–mesenchymal transition in the tumor. Our data identify a novel treatment with a combination of approved classes of drugs in preclinical breast cancer models. 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.
登录
查看更多内容
影响因子：
7.5
作者：
Ashrafi, Somayeh;Shapouri, Reza;Mahdavi, Mehdi
通讯作者：
Mahdavi, Mehdi
影响因子：
45.3
作者：
Barron, Thomas I.;Connolly, Roisin M.;Visvanathan, Kala
通讯作者：
Visvanathan, Kala
影响因子：
3.8
作者：
D'Arcy M;Fleming J;Robinson WR;Kirk EL;Perou CM;Troester MA
通讯作者：
Troester MA
影响因子：
4
作者：
Bimonte S;Barbieri A;Cascella M;Rea D;Palma G;Del Vecchio V;Forte CA;Del Prato F;Arra C;Cuomo A
通讯作者：
Cuomo A
影响因子：
11.5
作者：
Hwang, Ki-Tae;Kim, Jongjin;Hwang, Kyu Ri
通讯作者：
Hwang, Kyu Ri