Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, Memphis, TN, USA.
J Control Release. 2010 Apr 2;143(1):151-8. doi: 10.1016/j.jconrel.2009.12.028. Epub 2010 Jan 7.
A novel microtubule destabilizer, substituted methoxybenzoyl-ary-thiazole (SMART)-100, was synthesized, which showed good anticancer activity in HepG2 cells. SMART-100 was able to circumvent multidrug resistance (MDR) and effectively inhibited the growth of cell lines that overexpress P-glycoprotein (P-gp). SMART-100 inhibited P-gp activity, which may be responsible for its ability to overcome MDR. Since SMART-100 is poorly soluble in water, it was formulated in polyethylene-b-poly(D,L-lactide) (PEG-PLA) micelles. The solubility of SMART-100 was increased by more than 1.1x10(5) folds. SMART-100 loaded PEG-PLA micelles could effectively inhibit HepG2 cell growth and arrest cell cycle progression at G2/M phase, followed by appearance of a sub-G1 phase, which is indicative of cell apoptosis. Increased Caspase-3 activity was also observed when HepG2 cells were treated with SMART-100. The anticancer activity of SMART-100 loaded PEG-PLA micelles was also evaluated on luciferase expressing C4-2-Luc cell lines by IVIS imaging. Our results suggest that SMART-100 has the potential to treat resistant cancers.
一种新型的微管稳定剂，取代甲氧基苯甲酰-芳基噻唑（SMART）-100，被合成出来，它在 HepG2 细胞中显示出良好的抗癌活性。SMART-100 能够规避多药耐药（MDR），并有效地抑制过度表达 P-糖蛋白（P-gp）的细胞系的生长。SMART-100 抑制了 P-gp 的活性，这可能是它克服 MDR 的能力的原因。由于 SMART-100 在水中的溶解度较差，因此将其制成了聚乙二醇-b-聚（D，L-丙交酯）（PEG-PLA）胶束。SMART-100 的溶解度提高了超过 1.1x10(5)倍。负载 SMART-100 的 PEG-PLA 胶束能够有效地抑制 HepG2 细胞的生长，并将细胞周期阻滞在 G2/M 期，随后出现亚 G1 期，这表明细胞凋亡。当 HepG2 细胞用 SMART-100 处理时，也观察到 Caspase-3 活性的增加。SMART-100 负载的 PEG-PLA 胶束的抗癌活性也通过 IVIS 成像在表达荧光素酶的 C4-2-Luc 细胞系上进行了评估。我们的结果表明，SMART-100 有可能治疗耐药性癌症。
