负载紫杉醇和JAK2-STAT3抑制剂纳米载药系统对胃癌细胞生物活性的影响机制研究  

Influence Mechanism Study of Paclitaxel and JAK2-STAT3 Inhibitor Nanoscale Drug Carriers on the Biological Activity of Gastric Cancer Cells

作　　者：贾静[1] 马晓雷 张鹏[1] 耿倩雯[1] 胡楠 薛玲珑[1] JIA Jing;MA Xiaolei;ZHANG Peng;GENG Qianwen;HU Nan;XUE Linglong(Department of Gastroenterology,The Sixth Hospital of Shanxi Medical University,Taiyuan Shanxi 030008,China;School of Basic Medicine,Nanjing Medical University,Nanjing Jiangsu 211166,China)

机构地区：[1]山西医科大学第六医院消化内科,山西太原030008 [2]南京医科大学基础医学院,江苏南京211166

出　　处：《中国医疗设备》2024年第10期146-151,158,共7页China Medical Devices

基　　金：国家自然科学基金(81803247)。

摘　　要：目的研讨负载紫杉醇和JAK2-STAT3抑制剂纳米载药系统对胃癌细胞生物活性的抑制作用。方法选取胃癌细胞GBC-SD为研究对象,构建PLGA(TAXOL+AZD1480)纳米粒子,确定粒子的稳定性及释放药物速率稳定性;比较对照组、PLGA组、TAXOL+AZD1480组、PLGA(TAXOL+AZD1480组)各组胃癌细胞JAK2-STAT3信号通路活性、增殖、凋亡、迁移、侵袭能力。结果PLGA(TAXOL+AZD1480)纳米粒子120 h内呈现出缓慢、稳定释放;TAXOL+AZD1480组及PLGA(TAXOL+AZD1480)组JAK2、STAT3磷酸化蛋白水平均降低(P<0.05);与PLGA组相比,TAXOL组、AZD1480组均可以下调胃癌细胞增殖、迁移、侵袭能力,上调细胞凋亡能力,Cyclin D1、MMP-9蛋白表达受到抑制,Cleaved-caspase-3、Bax蛋白表达提升(P<0.05);与TAXOL组、AZD1480组相比,TAXOL+AZD1480组、PLGA(TAXOL+AZD1480)组进一步下调胃癌细胞增殖、迁移、侵袭能力,上调凋亡能力(P<0.05);TAXOL+AZD1480组、PLGA(TAXOL+AZD1480)组两组癌细胞增殖、凋亡、迁移、侵袭活性相近(P>0.05)。结论本研究成功构建了共载TAXOL和AZD1480的PLGA(TAXOL+AZD1480)载药传递系统,该纳米体系具有药物缓释以及抑制胃癌的作用,药效确切,值得在临床进一步推广。Objective To evaluate the inhibitory effect of paclitaxel(TAXOL)and JAK2-STAT3 inhibitor nanoscale drug carriers on the biological activity of gastric cancer cells.Methods Gastric cancer cell GBC-SD was selected as the research object,and PLGA(TAXOL+AZD1480)nanoparticles were constructed to determine the stability of the particles and drug release rate.The activity,proliferation,apoptosis,migration and invasion of JAK2-STAT3 signaling pathway of gastric cancer cells in the control,PLGA,TAXOL+AZD1480 and PLGA(TAXOL+AZD1480)groups were compared.Results The PLGA(TAXOL+AZD1480)nanoparticles released slowly and stably within 120 h.The levels of JAK2 and STAT3 phosphorylated protein in TAXOL+AZD1480 and PLGA groups were decreased(P<0.05).Compared with PLGA group,TAXOL group and AZD1480 group could down-regulate the proliferation,migration,invasion and up-regulated apoptosis of gastric cancer cells,and the expression of Cyclin D1 and MMP-9 proteins were inhibited,but Cleaved-caspase-3 and Bax proteins were increased(P<0.05).Compared with TAXOL group and AZD1480 group,TAXOL+AZD1480 group and PLGA(TAXOL+AZD1480)group further down-regulated the proliferation,migration and invasion abilities of gastric cancer cells,and up-regulated the apoptosis ability(P<0.05).The proliferation,apoptosis,migration and invasion activities of cancer cells in TAXOL+AZD1480 group and PLGA(TAXOL+AZD1480)group were similar(P>0.05).Conclusion The PLGA(TAXOL+AZD1480)nanoscale drug carriers co-loaded with TAXOL and AZD1480 has been successfully constructed.It has the effects of drug sustained release and gastric cancer inhibition,and its efficacy is definite,which is worthy of further clinical promotion.

关 键 词：胃癌 纳米颗粒 纳米药物载体 紫杉醇 PLGA TAXOL AZD1480 细胞活性 

分 类 号：R735.2[医药卫生—肿瘤]