The effects of naloxone on human breast cancer progression: in vitro and in vivo studies on MDA.MB231 cells.
The effects of naloxone on human breast cancer progression: in vitro and in vivo studies on MDA.MB231 cells.
复制标题
DOI：
10.2147/ott.s145780
复制
发表时间：
2018
影响因子：
4
通讯作者：
Cuomo A
中科院分区：
文献类型：
--
作者：
Bimonte S;Barbieri A;Cascella M;Rea D;Palma G;Del Vecchio V;Forte CA;Del Prato F;Arra C;Cuomo A
纳洛酮被认为是一种特异性竞争性阿片拮抗剂，作用于阿片受体（μ、δ和κ）水平，具有混合激动剂-拮抗剂或激动剂作用。纳洛酮在肿瘤细胞生长中的作用在人类癌细胞系中的研究很少。在本研究中，我们报告了体外和体内实验的结果，以评估纳洛酮对人乳腺癌细胞生长和进展的影响。对用不同浓度（10-100 μM）纳洛酮处理的雌激素受体阴性人乳腺癌细胞MDA. MB 231进行体外试验。在通过使用皮下注射到小鼠中的MDA.MB231产生的人三阴性乳腺癌的小鼠模型上进行体内实验。小鼠每天腹腔注射纳洛酮，剂量为0.357 mg/kg，持续2周，接下来的2周为0.714 mg/kg。通过将异硫氰酸荧光素-葡聚糖（100 μL）注射到小鼠尾静脉中检测微血管形成，并通过小鼠肿瘤切片上的CD 31免疫组织化学证实。体外实验表明，纳洛酮以剂量依赖方式抑制MDA.MB231细胞增殖，但增加细胞死亡。体内研究表明，只要给予纳洛酮，用纳洛酮治疗的小鼠的肿瘤显著小于在对照组中观察到的肿瘤。最后，纳洛酮不能损害治疗小鼠肿瘤中的微血管形成。我们的数据首次表明，纳洛酮在不影响血管生成的情况下减少了乳腺癌的进展。
Naloxone is viewed as a specific competitive opioid antagonist acting at the level of opioid receptors (μ, δ, and κ) with blended agonist-adversary or agonist action. The role of naloxone in tumor cell growth has been poorly studied in human cancer cell lines. In the present study, we report findings from in vitro and in vivo experiments performed to evaluate the effects of naloxone on human breast cancer cell growth and progression. In vitro assays were conducted on estrogen receptor-negative human breast carcinoma cells, MDA.MB231, treated with naloxone at different concentrations (10–100 μM). In vivo experiments were performed on a mouse model of human triple-negative breast cancer generated by using MDA.MB231 injected subcutaneously in mice. Naloxone was daily intraperitoneally injected in mice at 0.357 mg/kg for 2 weeks and at 0.714 mg/kg for the next 2 weeks. Microvessels formation was detected by fluorescein isothiocyanate-dextran (100 μL) injected into the tail vein of mice and confirmed by immunohistochemistry with CD31 on mice tumor sections. In vitro tests showed that the cell proliferation of MDA.MB231 was inhibited by naloxone in a dose-dependent manner, whereas the cell death was increased. In vivo studies demonstrated that tumors of mice treated with naloxone were significantly smaller than those observed in the control groups, as long as naloxone was administered. Finally, naloxone was not able to impair the microvessel formation in tumors of treated mice. Our data showed, for the first time, that naloxone reduced breast cancer progression without affecting angiogenesis.