Abstract：
The antitumor and antimetastatic activity of dopamine D2 receptor antagonists spiperone was studied in C57BL/6 mice in a model of combined pathology (emphysema and lung cancer). Emphysema was induced by administration of LPS and cigarette smoke extract. Lung cancer was induced by injection of Lewis lung carcinoma cells into the lung. It has been shown that under conditions of combined lung pathology, spiperone prevents inflammatory infiltration and emphysematous expansion of the lungs and reduces the size of the primary tumor node, the number of metastases, and the area of the lungs affected by metastases. Spiperone reduces the number of cancer stem cells (CSCs) in the lungs and blood of mice with combined pathology. CSCs isolated from the lungs and blood of mice with combined pathology treated with spiperone had a significantly lower potential to form a tumorosphere in vitro than CSCs from untreated mice with emphysema and lung carcinoma. Thus, blockade of dopamine D2 receptors is a promising approach for correcting combined lung pathology and can be used in the development of a method for treating lung cancer in patients with emphysema.
摘要：
在C57BL/6小鼠中，在联合病理（肺气肿和肺癌）模型中研究了多巴胺D2受体拮抗剂螺培酮的抗肿瘤和抗转移活性。通过施用LPS和香烟烟雾提取物诱导肺气肿。通过将Lewis肺癌细胞注射到肺中诱导肺癌。研究表明，在合并肺部病理的情况下，螺哌酮可防止肺部的炎症浸润和气肿性扩张，并减少原发性肿瘤淋巴结的大小。转移的数量，和受转移影响的肺部区域。Spiperone减少了具有联合病理的小鼠的肺和血液中的癌症干细胞（CSC）的数量。与未治疗的患有肺气肿和肺癌的小鼠的CSC相比，从用螺哌酮治疗的组合病理的小鼠的肺和血液中分离的CSC在体外形成肿瘤圈的可能性显着降低。因此，多巴胺D2受体的阻断是纠正合并肺部病理的有前途的方法，可用于开发治疗肺气肿患者肺癌的方法。
