载多烯紫杉醇脂质微泡增强人胰腺癌BxPC3细胞的增殖抑制和凋亡诱导作用

目的制备载多烯紫杉醇脂质超声微泡,并研究其联合超声靶向微泡破裂技术(UTMD)对人胰腺癌BxPC3细胞的增殖抑制和凋亡诱导作用。方法采用机械振荡法制备载多烯紫杉醇的脂质超声微泡,检测其粒径、zeta电位、载药量、包封率等性质,MTT法检测IC50,CCK-8法检测细胞毒性作用,流式细胞术检测细胞周期,Annexin V-FITC/PI双染法检测细胞凋亡率,TUNEL法检测细胞凋亡情况,并与单纯多烯紫杉醇药物组、多烯紫杉醇药物+超声组等进行比较。结果载多烯紫杉醇超声微泡平均粒径1.6μm,微泡的包封率为64.2%,平均载药量为16.1%;载多烯紫杉醇脂质微泡组的细胞毒性作用强于其他各组(P<0.01),细胞凋亡率高于其他各组(P<0.01);载多烯紫杉醇脂质微泡组G2/M期细胞增多,与其他组比较差异有统计学意义(P<0.01)。结论载多烯紫杉醇脂质微泡联合UTMD能够增加G2/M期细胞阻滞,增强对BxPC3细胞的增殖抑制和凋亡诱导作用;载多烯紫杉醇脂质微泡有望成为一种治疗胰腺癌的新型药物载体。

Enhanced proliferation inhibition and apoptosis-inducing effects of docetaxel-loaded lipid microbubble on human pancreatic cancer cells in vitro

Objective To investigate the proliferation inhibition and apoptosis-inducing effect of docetaxel-loaded lipid microbubble(DLLM) combined with ultrasound targeted microbubble destruction(UTMD) on human pancreatic cancer cells in vitro.Methods DLLM was prepared by mechanical vibration,and its physical properties were characterized.The median inhibitory concentration(IC50) of DLLM was determined with MTT assay,and its cytotoxicity evaluated with cell counting Kit-8(CCK-8) assay.The effects of docetaxel,DLLM,and DLLM combined with UTMD on cell cycle and apoptosis of BxPC3 cells were tested with flow cytometry(FCM) and TUNEL assay,respectively.Results DLLM had an average size of 1.6 μm,and the average drug entrapment efficiency and drug-loaded amount was 64.2% and 16.1%,respectively.Compared with the control groups,DLLM had a significantly enhanced cytotoxic effect(P<0.01) and caused an increased apoptosis rate in BxPC3 cells(P<0.01).Cell cycle analysis showed that DLLM combined with UTMD resulted in an significantly higher percentage of cells with G2/M phase arrest than the other treatments(P<0.01).Conclusions DLLM combined with UTMD can increase G2/M phase arrest and enhance the proliferation inhibition and apoptosis-inducing effect on BxPC3 cells,and can serve as an effective drug delivery system for pancreatic cancer therapy.