黑色素瘤是一种具有高转移活性的恶性皮肤肿瘤。虽然黑色素瘤已经被充分研究,它的细胞动力学仍然难以捉摸。胆囊收缩素(CCK)受体在各种类型的肿瘤中表达,因为CCK促进肿瘤细胞的存活和增殖。因此,我们假设黑色素瘤的生长受到CCK受体信号的正向调节,并试图研究CCK受体拮抗剂是否影响表达CCK受体的黑色素瘤细胞的生长.免疫组织化学,CCK受体A在黑色素瘤的临床标本中表达。CCK受体拮抗剂通过抑制细胞分裂和促进细胞凋亡来降低黑色素瘤细胞的活力。CCK受体拮抗剂还通过增强促凋亡蛋白的基因表达来降低线粒体膜电位,Bcl2相关X,和肿瘤抑制剂,p53,表明该拮抗剂以线粒体依赖性方式诱导黑色素瘤细胞凋亡。此外,caspase3抑制剂,Z-DEVD-FMK,部分阻断了拮抗剂的抗生存力,表明caspase3参与拮抗剂诱导的细胞凋亡。值得注意的是,对携带黑色素瘤的小鼠局部施用CCK受体拮抗剂后,肿瘤生长减弱.因此,我们的研究提示CCK受体拮抗剂在治疗皮肤癌方面的治疗潜力.
Melanoma is a malignant skin tumor with high metastatic activity. Although melanoma has been well-studied, its cellular kinetics remain elusive. The cholecystokinin (CCK) receptor is expressed in various types of tumors because CCK promotes the survival and proliferation of tumor cells. Thus, we hypothesized that the growth of melanoma was positively regulated by signals from the CCK receptor and sought to investigate whether CCK receptor antagonists affect the growth of melanoma cells expressing CCK receptor. Immunohistochemically, the CCK receptor A is expressed in the clinical specimens of melanoma. CCK receptor antagonists decreased the viability of melanoma cells by suppressing cell division and promoting apoptosis. CCK receptor antagonists also decreased the mitochondrial membrane potential through enhanced gene expression of the proapoptotic protein, Bcl2-associated X, and tumor suppressor, p53, suggesting that the antagonist induced the apoptosis of melanoma cells in a mitochondria-dependent manner. In addition, a caspase 3 inhibitor, Z-DEVD-FMK, partially blocked the antiviability of the antagonist, indicating that caspase 3 is involved in antagonist-induced apoptosis. Notably, tumor growth was attenuated when a CCK receptor antagonist was locally administered to the melanoma-bearing mice. Therefore, our study suggests the therapeutic potential of CCK receptor antagonists in the treatment of skin cancer.