Piceatannol (PIC) is known to have anticancer activity, which has been attributed to its ability to block the proliferation of cancer cells via suppression of the NF-kB signaling pathway. However, its effect on hypoxia-inducible factor (HIF) is not well known in cancer. In this study, PIC was loaded into bovine serum albumin (BSA) by desolvation method as PIC-BSA nanoparticles (NPs). These PIC-BSA nanoparticles were assessed for in vitro cytotoxicity, migration, invasion, and colony formation studies and levels of p65 and HIF-1α. Our results indicate that PIC-BSA NPs were more effective in downregulating the expression of nuclear p65 and HIF-1α in colon cancer cells as compared to free PIC. We also observed a significant reduction in inflammation induced by chemical colitis in mice by PIC-BSA NPs. Furthermore, a significant reduction in tumor size and number of colon tumors was also observed in the murine model of colitis-associated colorectal cancer, when treated with PIC-BSA NPs as compared to free PIC. The overall results indicate that PIC, when formulated as PIC-BSA NPs, enhances its therpautice potential. Our work could prompt further research in using natural anticancer agents as nanoparticels with possiable human clinical trails. This could lead to the development of a new line of safe and effective therapeutics for cancer patients.

译文

:哌替卡诺醇(PIC)已知具有抗癌活性,这归因于其通过抑制NF-kB信号通路来阻止癌细胞增殖的能力。然而,其对缺氧诱导因子(HIF)的作用在癌症中尚不为人所知。在这项研究中,通过去溶剂化方法将PIC作为PIC-BSA纳米颗粒(NPs)加载到牛血清白蛋白(BSA)中。评估了这些PIC-BSA纳米粒子的体外细胞毒性,迁移,侵袭和集落形成研究以及p65和HIF-1α的水平。我们的结果表明,与游离PIC相比,PIC-BSA NPs在下调结肠癌细胞中核p65和HIF-1α的表达方面更有效。我们还观察到由PIC-BSA NPs引起的化学性结肠炎在小鼠中引起的炎症显着减少。此外,与游离PIC相比,当用PIC-BSA NPs治疗时,在结肠炎相关大肠癌的鼠模型中,还观察到肿瘤大小和结肠肿瘤数量的显着减少。总体结果表明,当PIC配制成PIC-BSA NP时,可以增强其治疗潜力。我们的工作可能会促使人们进一步研究将天然抗癌药用作可能与人类临床试验结合使用的纳米颗粒。这可能会导致开发出针对癌症患者的安全有效的新疗法系列。

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