Research Institute of General Pathology and Pathophysiology, Moscow, Russia.
Bull Exp Biol Med. 2024 Jul;177(3):368-373. doi: 10.1007/s10517-024-06191-z. Epub 2024 Aug 12.
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.
多巴胺 D2 受体拮抗剂 spiperone 的抗肿瘤和抗转移活性在 LPS 和香烟烟雾提取物诱导的肺气肿和肺癌联合模型的 C57BL/6 小鼠中进行了研究。肺癌通过向肺部注射 Lewis 肺癌细胞诱导。结果表明，在联合肺部病理条件下，spiperone 可防止肺部炎症浸润和肺气肿扩张，并减少原发性肿瘤节点的大小、转移的数量以及受转移影响的肺部面积。spiperone 减少了联合病理学小鼠肺部和血液中的癌症干细胞 (CSC) 的数量。与未经治疗的肺气肿和肺癌小鼠的 CSCs 相比，用 spiperone 处理的联合病理学小鼠的肺部和血液中分离出的 CSCs 在体外形成肿瘤球体的能力明显降低。因此，多巴胺 D2 受体阻断是纠正联合肺部病理的一种很有前途的方法，并可用于开发治疗肺气肿患者肺癌的方法。
