Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Vojvode Stepe 444a, 11042 Belgrade, Serbia.
Department of Science, Institute of Information Technologies, University of Kragujevac, Jovana Cvijica bb, 34000 Kragujevac, Serbia.
Molecules. 2022 Mar 25;27(7):2115. doi: 10.3390/molecules27072115.
Pancreatic carcinoma still represents one of the most lethal malignant diseases in the world although some progress has been made in treating the disease in the past decades. Current multi-agent treatment options have improved the overall survival of patients, however, more effective treatment strategies are still needed. In this paper we have characterized the anticancer potential of coumarin-palladium(II) complex against pancreatic carcinoma cells. Cells viability, colony formation and migratory potential of pancreatic carcinoma cells were assessed in vitro, followed by evaluation of apoptosis induction and in vivo testing on zebrafish. Presented results showed remarkable reduction in pancreatic carcinoma cells growth both in vitro and in vivo, being effective at micromolar concentrations (0.5 μM). Treatments induced apoptosis, increased / ratio and suppressed the expression of and , genes shown to be significantly up-regulated in pancreatic ductal adenocarcinoma. Importantly, treatments of the zebrafish-pancreatic adenocarcinoma xenografts resulted in significant reduction in tumor mass, without provoking any adverse toxic effects including hepatotoxicity. Presented results indicate the great potential of the tested compound and the perspective of its further development towards pancreatic cancer therapy.
尽管在过去几十年中在治疗这种疾病方面取得了一些进展,但胰腺癌仍然是世界上最致命的恶性疾病之一。目前的多药物治疗方案提高了患者的总体生存率,但仍需要更有效的治疗策略。在本文中,我们研究了香豆素-钯(II)配合物对胰腺癌细胞的抗癌潜力。在体外评估了胰腺癌细胞的细胞活力、集落形成和迁移能力,然后在斑马鱼上进行了凋亡诱导评估和体内测试。结果表明,该配合物在体外和体内均能显著抑制胰腺癌细胞的生长,其有效浓度为微摩尔级(0.5 μM)。处理诱导了细胞凋亡,增加了 / 比值,并抑制了基因和基因的表达,这些基因在胰腺导管腺癌中明显上调。重要的是,对斑马鱼胰腺腺癌异种移植的处理导致肿瘤质量显著减少,而没有引起任何不良反应,包括肝毒性。研究结果表明,该化合物具有很大的潜力,有望进一步开发用于胰腺癌治疗。