超声微泡运载基因磁性脂质造影剂联合磁感应热疗对肝癌HepG2细胞增殖活性的影响

Effects on the combination of magnetic lipid contrast agent of ultrasound micro-bubbles with carrier gene and magnetic induction hyperthermia on proliferation of HepG2 cells of hepatocellular carcinoma

目的:研究超声微泡运载基因磁性脂质造影剂联合磁感应热疗对肝癌HepG2细胞增殖活性的影响。方法:将HepG2细胞随机分为A组、B组和C组,A组加入1640培养液,B组加入超声微泡运载基因磁性脂质造影剂,C组在B组基础上置于高频加热器平板线圈上1 h,分析3组对肝癌HepG2细胞增殖活性的影响。结果:运载基因磁性脂质超声微泡显微镜下观察超声微泡大小均一,分布均匀,激光激发后周围呈现绿色荧光,体外靶向与肝癌HepG2细胞紧密结合;磁场强度恒定条件下,运载基因磁性脂质超声微泡升温能力与Fe_3O_4磁性纳米粒子浓度呈正相关;B组和C组与A组相比较对肝癌细胞HepG2增殖均有抑制作用,其差异有统计学意义(x^2=4.015,x^2=16.281;P<0.05);B组和C组凋亡率显著高于A组,且C组凋亡情况最为显著,其差异有统计学意义(x^2=20.318,x^2=40.549;P<0.001)。结论:制备的可以携带目的基因的超声场及磁场的双靶向超声微泡,对肿瘤进行磁感应热疗,可提高转染效率,有效抑制肝癌HepG2细胞增殖,为肿瘤靶向治疗提供新思路。

Objective: To study the effect on combination of magnetic lipid contrast agent with carrier gene and magnetic induction hyperthermia on the proliferation of HepG2 cells of hepatocellular carcinoma. Methods: HepG2 cells were randomly divided into group A, group B and group C. Group A was treated with 1640 medium, and group B with magnetic lipid contrast agent of ultrasound micro-bubbles with carrying gene, and Group C was treated with SP-04C high frequency heater coil on MFH plate for 1 hour on the basis of group B. The influences of three groups on the proliferation activity of HepG2 cells of hepatocellular carcinoma were compared and analyzed. Results: Under the white light, ultrasound micro-bubbles with carrier gene were uniform in size and its distribution was homogeneous, and its periphery appeared green fluorescence after laser was stimulated. And target cells were closely bound to HepG2 cells in vitro. Under constant magnetic field intensity, the warming ability of magnetic lipid micro-bubbles was positively correlated with the concentration of Fe3O4 magnetic nanoparticles. Compared with group A, group B and group C had significantly inhibiting effects on proliferation of HepG2 cells of hepatocellular carcinoma (x^2=4.015, x^2=16.281, P<0.05). And the apoptosis rate of group B and C were significantly higher than those of group A, respectively, and the apoptosis rate of group C was the most significant (x^2=20.318, x^2=40.549, P<0.001). Conclusion: This dualtargeted ultrasound micro-bubbles with target gene of ultrasound field and magnetic field, which has been successfully prepared to implement magnetic induction hyperthermia for carcinoma, and can increase transfection efficiency, and can effectively inhibit the proliferation of HepG2 cells of hepatocellular carcinoma. Therefore, it provides a new idea for targeted therapy of carcinoma.