瘤内注射紫杉醇脂质体对小鼠H22移植瘤抑制作用的研究

目的比较瘤内注射和静脉注射紫杉醇脂质体对小鼠H22肝细胞癌皮下移植瘤的抑瘤作用，探讨瘤内注射微球化疗药物应用的可行性。方法采用ICR小鼠建立H22皮下移植瘤模型，随机分为瘤内注射紫杉醇脂质体组（IT-PL）、静脉注射紫杉醇脂质体组（IV-PL）和瘤内注射5％葡萄糖溶液组（IT-GS）。10天后待瘤体生长至直径10mm左右，分别予经超声引导瘤内注药及尾静脉给药处理。紫杉醇脂质体的给药浓度为3mg／ml，剂量为75mg／kg，每周1次，共2周。采用近红外荧光活体显像法观察注药24h内药物在小鼠体内的分布情况。隔日记录瘤体积变化并观察小鼠的不良反应，计算各组的抑瘤率。瘤体组织石蜡包埋后行HE染色。结果超声引导下瘤内注射紫杉醇脂质体时，针头附近区域见回声增高有助于确认药物分布于瘤体内。近红外荧光活体显像示瘤内注射24h药物持续集中在瘤体内，无明显全身分布；静脉注射药物则逐渐集中至瘤体，但瘤体内的药物浓度低于瘤内注射组。IT-PL组与IV-PL组的抑瘤率分别为95.0％和56.1％，差异有统计学意义（P＜0.05）。病理组织学检查示IT GS组的肿瘤细胞生长旺盛，而IT-PL组的瘤体内及周边有脂质沉积，仅边缘少量残存肿瘤细胞。瘤内注射部位皮下组织未见溃破、糜烂；未观察到明显全身不良反应。结论紫杉醇脂质体瘤内注射有可能成为针对局部实体肿瘤安全、有效的给药模式。

Tumor suppressive efficacy of paclitaxel liposome by intratumoral injection in mice H22 xenograft tumor models

Objective To compare the tumor suppressive efficacy of paclitaxel liposome through intratumoral injection in mice H22 xenograft tumor models with that through intravenous injection and discuss the possibility of applying microsphere drug agents in the intratumoral chemotherapy.Methods H22 subcutaneous xenograft tumor models were established in ICR mice and distributed randomly into 3 groups with intratumoral injection of 5% glucose solution（IT-GS,control group）,intravenous injection of paclitaxel liposome（IV-PL） and intratumoral injection of paclitaxel liposome（IT-PL）.When tumor diameter reached 10mm at 10＋ days post-treatment,intratumoral injection guided by ultrasonography and intravenous injection through tail vein were given separately once a week in the following two weeks.The in vivo near-infrared fluorescence imaging was used to indicate the drug distribution in mice within 24h after administration.The paclitaxel liposome with concentration of 3mg/ml was administered at a dose of 75mg/kg.Adverse effect and tumor volume change were observed and recorded every other day.Mice were executed on the 14th day of treatment.The tumors were excised,weighted,embedded in paraffin and then stained with HE for futher pathologic analysis.Results Increased echogenicity could be detected by ultrasonography when paclitaxel liposome was injected intratumorally,ensuring that the drug distributed in the tumor.The in vivo near-infrared fluorescence imaging displayed a sustained high drug concentration confined in tumor for 24 hours after intratumoral injection,while a gradually increasing and relatively low concentration of drug in tumor after intravenous injection.The tumor regression rates of IT-PL group and IV-PL group were 95.0% and 56.1% with statistical significance（P0.05）.The following pathologic examination under microscope revealed that densely growing malignant tumor cells were found in control group while in IT-PL group there was lipid deposition around and inside the tumor and a relatively small amount of residual tumor cells could be found on the edge.Nevertheless,the vitality of the mice in IT-PL group was the best among the 3 groups.No obvious diabrosis or erosion of subcutaneous tissues and overall adverse effect were observed in IT-PL group.Conclusion These results indicate that the intratumoral injection of paclitaxel liposome would be a safe and effective method in the treatment of local solid tumors.