Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
Department of Pharmaceutics & Industrial Pharmacy, Faculty of Pharmacy, Minia University, Minia 61519, Egypt.
Int J Mol Sci. 2019 Nov 18;20(22):5788. doi: 10.3390/ijms20225788.
Research on statins highlights their potent cytotoxicity against cancer cells and their potential for cancer prevention. The aim of the current study was to examine whether loading lovastatin (LVS) in zein (ZN) nanoparticles (NPs) would potentiate the anti-proliferative effects of LVS and enhance its proliferation-inhibiting activity in HepG2 cells. LVS-ZN NPs were prepared and showed excellent characteristics, with respect to their particle size, zeta potential, diffusion, and entrapment efficiency. In addition, they showed the most potent anti-proliferative activity against HepG2 cells. ZN alone showed an observable anti-proliferative that was significantly higher than that of raw LVS. Furthermore, LVS uptake by HepG2 cells was greatly enhanced by the formulation in ZN. A cell cycle analysis indicated that LVS induced a significant cell accumulation in the G2/M and pre-G phases. In this regard, the LVS-ZN NPs exhibited the highest potency. The accumulation in the pre-G phase indicated an enhanced pro-apoptotic activity of the prepared formula. The cells incubated with the LVS-ZN NPs showed the highest percentage of cells with annexin-V positive staining. In addition, the same incubations showed the highest content of caspase-3 enzyme in comparison to raw LVS or ZN. Thus, the loading of LVS in ZN nanoparticles enhances its anti-proliferative activity against HepG2 cells, which is attributed, at least partly, to the enhanced cellular uptake and the induction of apoptosis.
研究他汀类药物突出了它们对癌细胞的强大细胞毒性及其预防癌症的潜力。本研究的目的是研究将洛伐他汀（LVS）载入玉米醇溶蛋白（ZN）纳米颗粒（NPs）中是否会增强 LVS 的抗增殖作用，并增强其在 HepG2 细胞中的增殖抑制活性。制备了 LVS-ZN NPs，其粒径、Zeta 电位、扩散和包封效率均表现出优异的特性。此外，它们对 HepG2 细胞表现出最强的抗增殖活性。ZN 本身就表现出明显的抗增殖作用，明显高于原 LVS。此外，ZN 中的配方极大地增强了 HepG2 细胞对 LVS 的摄取。细胞周期分析表明，LVS 诱导细胞在 G2/M 和 Pre-G 期显著积累。在这方面，LVS-ZN NPs 表现出最高的效力。在 Pre-G 期的积累表明所制备的配方具有增强的促凋亡活性。与原 LVS 或 ZN 相比，用 LVS-ZN NPs 孵育的细胞显示出 annexin-V 阳性染色的细胞比例最高。此外，相同的孵育显示出最高含量的 caspase-3 酶。因此，将 LVS 载入 ZN 纳米颗粒中增强了其对 HepG2 细胞的抗增殖活性，这至少部分归因于增强的细胞摄取和诱导凋亡。
