Pharmaceutics Division, CSIR-Central Drug Research Institute, Lucknow, U.P., India.
Endocrinology Division, CSIR-Central Drug Research Institute, Lucknow, U.P., India.
Nanomedicine. 2017 Aug;13(6):1953-1963. doi: 10.1016/j.nano.2017.04.014. Epub 2017 Apr 27.
Survivin is up-regulated in 83% of endometrial cancer leading to resistance development. As endometrial tumor advances, it also elicits chronic inflammation characterized by increased cytokine secretion and immune cells infiltration. The present study was designed to engineer mixed micellar curcumin loaded formulation for investigating survivin down-regulation, its anti-cancer and cytokine modulatory potential against endometrial cancer Ishikawa cells. Flory-Huggins interaction parameter (χ) was applied to predict the compatibility between curcumin and surfactant mixture. The developed and characterized formulations were used to comparatively assess hemolysis, cellular uptake, cell-viability, apoptosis, mitochondrial membrane potential loss, rhodamine accumulation and bioavailability. In-vitro cytotoxicity in Vero cells demonstrated no deleterious effects on cell population. We saw better bioavailability, significant rhodamine accumulation, changes in protein expression and modulation in TNF-α, IL-6 and IL-10 levels. In conclusion, developed formulation warrants exploring the therapeutic interventions for overcoming resistance development in endometrial cancer.
Survivin 在 83%的子宫内膜癌中上调，导致耐药性的发展。随着子宫内膜肿瘤的进展，它还会引发慢性炎症，表现为细胞因子分泌增加和免疫细胞浸润。本研究旨在设计载姜黄素混合胶束给药系统，研究其对子宫内膜癌细胞 Ishikawa 的 survivin 下调作用、抗癌作用和细胞因子调节作用。采用 Flory-Huggins 相互作用参数（χ）预测姜黄素与表面活性剂混合物的相容性。对所制备的制剂进行了表征，并用于比较溶血、细胞摄取、细胞活力、细胞凋亡、线粒体膜电位丧失、罗丹明积累和生物利用度的评估。在 Vero 细胞中的体外细胞毒性实验表明，对细胞群体没有不良影响。我们观察到更好的生物利用度、显著的罗丹明积累、蛋白表达的变化以及 TNF-α、IL-6 和 IL-10 水平的调节。总之，所开发的制剂为探索治疗干预子宫内膜癌耐药性发展提供了依据。
