Department of Pathophysiology, College of Basic Medical Sciences, Jilin University, 126 Xinmin Street, Changchun, 130021, Jilin, PR China.
Department of Gynaecology and Obstetrics, The Second Hospital of Jinlin University, 218 Ziqiang Street, Changchun, 130041, Jilin, PR China.
Cancer Lett. 2019 Apr 28;448:1-10. doi: 10.1016/j.canlet.2019.01.002. Epub 2019 Jan 20.
Globally, prostate cancer remains a challenging health burden for men as it is the second leading cause of cancer death in men and about one in nine will be diagnosed with prostate cancer in his lifetime. Enhanced expression of COX-2 and Glut-1 proteins are reported as major factors leading to the origin and progress of prostate cancer through modulating the associated signaling pathways. In this study, we have synthesized a multifunctional liposomal system containing celecoxib and genistein drugs. The combinatorial effect of these drugs leads to the selectively induce the apoptosis of prostate cancer cells than normal fibroblast cells. The mechanistic study suggests that enhanced reactive oxygen species (ROS) formation and a decrease in cellular GSH concentration, along with inhibition of COX-2 synthesis and Glut-1 receptors are the key processes behind the inhibition of prostate cancer cells. Overall, these results provide strong evidence for the role of COX-2 and Glut-1 proteins for the progression of prostate cancer and highlighting the potential of celecoxib and genistein as a useful and combinatorial pharmacological agent for chemotherapeutic purposes in prostate cancer.
在全球范围内，前列腺癌仍然是男性面临的一项具有挑战性的健康负担，因为它是男性癌症死亡的第二大主要原因，大约每九名男性中就有一名会在其一生中被诊断出患有前列腺癌。COX-2 和 Glut-1 蛋白的过表达被报道为导致前列腺癌起源和进展的主要因素，通过调节相关信号通路。在这项研究中，我们合成了一种含有塞来昔布和金雀异黄素药物的多功能脂质体系统。这些药物的联合作用导致选择性诱导前列腺癌细胞凋亡，而正常成纤维细胞不受影响。机制研究表明，增强的活性氧（ROS）形成和细胞内 GSH 浓度的降低，以及 COX-2 合成和 Glut-1 受体的抑制，是抑制前列腺癌细胞的关键过程。总的来说，这些结果为 COX-2 和 Glut-1 蛋白在前列腺癌进展中的作用提供了有力证据，并强调了塞来昔布和金雀异黄素作为一种有用的联合药物在前列腺癌化疗中的潜力。
