Song Rong-Feng, Li Xiao-Jun, Cheng Xiao-Liang, Fu Ai-Rong, Wang Yan-Hua, Feng Yan-Jun, Xiong Yan
Department of Gastroenterology, Cancer Hospital of Jiangxi Province, Nanchang, Jiangxi 330029, P.R. China.
Department of Hepatic Neoplasms Surgery, Cancer Hospital of Jiangxi Province, Nanchang, Jiangxi 330029, P.R. China.
Oncol Rep. 2014 Oct;32(4):1481-8. doi: 10.3892/or.2014.3344. Epub 2014 Jul 21.
Gastroenteric cancer is one of the most prevalent cancers and is responsible for most cancer-related deaths worldwide. Paclitaxel (PTX), a classical microtubule inhibitor, is indicated in the treatment of gastric/gastroenteric cancers. In the present study, trimethyl chitosan (TMC)-loaded PTX (TMC-PTX) was prepared and evaluated for its therapeutic effect in gastric cancers. A spherical shaped nanosized TMC-PTX particle was formed with high loading capacity (30%) for PTX. The nanoparticles (NPs) showed a sustained release pattern (70%) for up to 96 h of study period. The positively charged NPs were preferentially internalized by Caco-2 cells. TMC-PTX inhibited the gastric cell proliferation with an IC50 value of 0.6 µg in NCI-N87 cells while it was 1.26 µg in the SGC-7901 cell line after 24 h exposure. The apoptosis assay (Annexin V/PI) showed a large presence of cells in the early and late apoptosis chamber, while cell cycle analysis showed a marked G2/M phase arrest (50-60%) in NCI-N87 and SGC-7901 cell lines indicating its potent anti-proliferative effect. The in vivo antitumor study in NCI-N87 and SGC-7901 bearing xenograft model showed a superior chemotherapeutic efficacy for TMC-PTX NP. The NP group significantly reduced the tumor growth with no obvious sign of systemic side-effects (safety). Collectively, our results suggest that the microtubule inhibitory effect of PTX-loaded polymer NP could be a promising system for the treatment of gastroenteric cancers.
胃肠癌是最常见的癌症之一，也是全球大多数癌症相关死亡的原因。紫杉醇（PTX）是一种经典的微管抑制剂，可用于治疗胃癌/胃肠癌。在本研究中，制备了负载三甲基壳聚糖（TMC）的PTX（TMC-PTX），并评估了其对胃癌的治疗效果。形成了球形纳米级TMC-PTX颗粒，对PTX具有高负载能力（约30%）。在长达96小时的研究期间，纳米颗粒（NPs）呈现出持续释放模式（约70%）。带正电荷的NPs被Caco-2细胞优先内化。TMC-PTX抑制胃癌细胞增殖，在NCI-N87细胞中IC50值为0.6μg，而在SGC-7901细胞系中暴露24小时后为1.26μg。凋亡检测（Annexin V/PI）显示早期和晚期凋亡腔室中有大量细胞，而细胞周期分析显示NCI-N87和SGC-7901细胞系中明显的G2/M期阻滞（50-60%），表明其具有强大的抗增殖作用。在携带NCI-N87和SGC-7901异种移植模型的体内抗肿瘤研究中，TMC-PTX NP显示出卓越的化疗效果。NP组显著降低了肿瘤生长，没有明显的全身副作用迹象（安全性）。总体而言，我们的结果表明，负载PTX的聚合物NP的微管抑制作用可能是一种有前途的胃肠癌治疗系统。
