RGD偶联吉西他滨白蛋白纳米粒对胰腺癌细胞周期和凋亡的影响

摘要

背景与目的:吉西他滨作为目前临床胰腺癌一线用药,由于其化疗耐药性,化疗效果较差.本研究通过制备RGD偶联吉西他滨白蛋白纳米粒,通过增加其靶向性,探讨其对胰腺癌细胞株BxPC-3和PANC-1细胞周期和凋亡的影响.方法:以人胰腺癌细胞株BxPC-3(高表达αVβ3受体)和PANC-1(低表达αVβ3受体)为研究对象,各分为6个给药组:对照组、BSANP(白蛋白纳米粒)、RGD-BSANP组、BSANP-GEM组、GEM原药组(吉西他滨)、RGD-BSANP-GEM组.运用PI单染检测给药后24 h细胞周期的变化,Annexin V/PI双染色法检测细胞凋亡.结果:在BxPC-3细胞株中,与BSANP-GEM组及GEM组相比,RGD-BSANP-GEM组S期细胞比例明显下降,G0/G1期细胞比例明显增多,且在RGD-BSANP-GEM组凋亡率最高:而在PANC-1细胞中,RGD-BSANP-GEM组Go/G1期细胞阻滞的比例和凋亡率低于BxPC-3细胞株.结论:RGD环肽能够增加BSANP-GEM对高表达αVB 3胰腺癌BxPC-3细胞G0/G1期阻滞及细胞凋亡.%Background and purpose: Although gemcitabine is the first line chemotherapeutic agents in pancreatic cancer, it acquires poor efficiency due to its chemoresistance. This study developed RGD-conjugated gemcitabine-loaded albumin nanoparticles and then explored the effect of RGD-conjugated gemcitabine-loaded albumin nanoparticles on cell cycle and apoptosis of BxPC-3 and PANC-1 cells. Methods: Human pancreatic carcinoma BxPC-3 and PANC-1 cells were cultured and then treated with blank albumin nanoparticles, RGD-conjugated albumin nanoparticles, gemcitabine-loaded albumin nanoparticles, pure gemcitabine and RGD-conjugated gemcitabine-loaded albumin nanoparticles respectively. The cell cycle of cells was analyzed by propidium iodide (PI) staining. The cell apoptosis was detected by both Annexin V and PI staining. Results: In BxPC-3 cells, we demonstrated significantly higher apoptosis and G0/G1 arrest in RGD-conjugated gemcitabine-loaded nanoparticles treatment group. Conclusion: RGD peptides can increase cell apoptosis and G0/G1 arrest of gemcitabine-loaded nanoparticles in BxPC-3 cells with high αvβ3 receptor expression.