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目的探讨载多烯紫杉醇(docetaxel,DTX)的靶向脂质超声微泡(DR5-DLLM)联合超声靶向微泡破裂技术(ultrasound targeted microbubble destruction,UTMD)对人肝癌Hep G2细胞增殖及凋亡的影响。方法采用机械振荡法、生物素-亲和素连结法分别制备包载DTX的脂质超声微泡(DLLM)和DR5-DLLM。MTT法检测DTX对人肝癌Hep G2细胞增殖的影响,计算半数抑制浓度(IC50)。将体外培养人肝癌Hep G2细胞分为空白对照组、DTX组、DTX+UTMD组、DLLM+UTMD组及DR5-DLLM+UTMD组,按IC50的药物浓度进行给药,UTMD以0.5 W/cm2的超声声强辐照45 s。CCK-8法检测细胞毒性作用,TUNEL法检测细胞凋亡情况,流式细胞术检测细胞周期。结果 DTX可有效抑制人肝癌Hep G2细胞增殖,且呈时间-剂量效应关系。与其他组比较,DR5-DLLM+UTMD组细胞毒性明显增强(P<0.001);细胞凋亡率明显升高(P<0.001);G2/M期细胞明显增多、S期细胞明显减少(P<0.001)。结论DR5-DLLM联合UTMD可增强对人肝癌Hep G2细胞增殖抑制、细胞周期阻滞和凋亡诱导作用,该方法有望成为肝癌分子靶向治疗的一种新途径。
Objective To investigate the effects of ultrasound-targeted microbubble destruction (UTMD) combined with drug-loaded lipid microbubble (DT5) -mediated lipid ultrasound microbubbles (DR5-DLLM) on proliferation and apoptosis of Hep G2 cells Impact. Methods DTX-loaded lipid ultrasound microbubbles (DLLMs) and DR5-DLLMs were prepared by mechanical shaking and biotin-avidin conjugation. The effect of DTX on the proliferation of human hepatocellular carcinoma Hep G2 cells was detected by MTT assay, and the half inhibitory concentration (IC50) was calculated. The Hep G2 cells cultured in vitro were divided into blank control group, DTX group, DTX + UTMD group, DLLM + UTMD group and DR5-DLLM + UTMD group according to IC50 drug concentration. UTMD was administered at 0.5 W / cm2 Ultrasound intensity irradiation 45 s. Cytotoxicity was detected by CCK-8 assay, apoptosis was detected by TUNEL assay, and cell cycle was detected by flow cytometry. Results DTX could effectively inhibit the proliferation of Hep G2 cells in a time-dose-dependent manner. Compared with other groups, the cytotoxicity was significantly increased in DR5-DLLM + UTMD group (P <0.001), the apoptosis rate was significantly increased (P <0.001), the number of G2 / M phase was significantly increased and the number of S phase was significantly decreased (P < 0.001). Conclusion DR5-DLLM combined with UTMD can enhance the proliferation inhibition, cell cycle arrest and apoptosis induction of human hepatocellular carcinoma Hep G2 cells. This method is expected to become a new molecular target therapy for hepatocellular carcinoma.