芒果苷脂质体的制备及其在Lewis肺癌移植瘤中的抗肿瘤作用及临床意义

Preparation of mangiferin liposome and its antitumor effect on transplanted Lewis lung carcinoma and its clinical significance

目的探讨水溶性芒果苷脂质体对Lewis肺癌的治疗作用。方法采用薄膜法制备芒果苷脂质体,并对其形态粒径进行表征。MTT法测定其对Lewis肺癌细胞的抗增殖作用;流式细胞术测定其对Lewis肺癌细胞凋亡作用的影响;建立小鼠Lewis肺癌移植瘤模型,检测芒果苷脂质体体内抗肿瘤效果并采用。TUNEL法原位测定其对凋亡的影响。结果芒果苷脂质体为均匀的球状或近球状,平均粒径为(207.2±2)nm。MTT实验结果显示,芒果苷脂质体对Lewis肺癌细胞抑制作用显著高于游离芒果苷(P<0.05),与Lewis肺癌细胞作用12 h后芒果苷IC_(50)为(45.2±5.1)μg/ml,芒果苷脂质体IC_(50)为(32.7±4.6)μg/ml。作用24 h后,芒果苷IC_(50)为(22.0±3.9)μg/ml,芒果苷脂质体IC_(50)为14.8±2.7μg/ml。而芒果苷脂质体在体内动物实验中同样表现出抗肿瘤活力,结果显示通过小鼠尾静脉给药后,可显著抑制Lewis移植瘤在小鼠体内的生长并且与对照组相比可延长生存期超过3 d。同时,流式细胞术分析Lewis细胞凋亡实验及TUNEL法原位检测肿瘤组织细胞凋亡结果均显示芒果苷脂质体可以诱导Lewis肺癌细胞凋亡。结论芒果苷脂质体可用于静脉注射改善芒果苷水溶性问题,同时提高其抗肿瘤效应。

Objective To prepare water soluble mangiferin liposome and observe its effect on inhibiting the growth of transplanting Lewis lung carcinoma. Method Mangiferin liposome was prepared by film dispersion methodo. The shape,particles size of the liposome was characterized. Anti-proliferation and apoptosis effects induced by mangiferin liposome on the Lewis lung carcinoma cells were determined by MTT method and flow cytometric analysis in vitro. The model of mice carried Lewis lung carcinoma was established.The effect of mangiferin liposome on anti-tumor and apoptosis in vivo was investigated. Result The result of electromicrography showed that the liposomes consisted of small spherical or similar to spherical. The average diameter of mangiferin liposome was 207. 2 ± 2 nm. Meanwhile,the results of MTT indicated that Mangiferin liposome could more effective inhibit the proliferation of Lewis lung carcinoma than free Mangiferin（ P0.05）.The IC_（50） of Mangiferin liposome is 32. 7 ± 4. 6 μg/ml on 12 h after Mangiferin treatment and the IC_（50） of free Mangiferin is 45.2±5.1 μg/ml on the same time point. 24 hours later,the IC_（50） of Mangiferin liposome is14.8±2.7 μg/ml. In contrast,the IC_（50） of free Mangiferin is 22.0± 3.9 μg/ml. The results in vivo also exhibited the anti-tumor effect of Mangiferin liposmes. Mangiferin liposmes could suppressed tumor growth efficiently and prolong the survival time more than 3days as control group. Furthermore,both flow cytometry of Lewis cell and TUNEL assay indiacated that mangiferin liposomes could induce apoptosis of Lewis lung carcinoma cells both in vitro and in vivo in our studies. Conclusion Liposome delivery system could effectively improve water solubility of mangiferin,and promote the anti-tumor effect.