CAJ | 학술논문

目的制备载10-羟基喜树碱(10-HCPT)脂质超声微泡(10-hydroxycamptothecine-loaded liposome microbubbles,HLM),并研究超声定位辐照载药微泡对H22移植瘤的生长抑制效应.方法制备载10-HCPT的脂质微泡及空白脂质微泡,建立小鼠肝癌H22实体瘤模型,将荷瘤鼠随机分为A、B两大组,每组又分为HLM组、10-HCPT注射液组、空白脂质微泡组和生理盐水对照组,经小鼠尾静脉输入药物或微泡后立即以治疗超声辐照瘤体部位,连续治疗7 d.A组小鼠治疗结束后剥取瘤块称重.计算抑瘤率,并作病理切片分析肿瘤微血管密度(MVD)变化;从治疗当天起,描绘B组小鼠肿瘤生长曲线,并观察生存期.结果 HLM组抑瘤率明显高于其他各组,MVD较其他组低(P<0.05),该组小鼠生存天数较对照组明显延长(P<0.01),但与10-HCPT注射液组比较差异无统计学意义(P>0.05);空白微泡组各检测指标与对照组差异无统计学意义(P>0.05).结论超声靶向破坏载药微泡可显著提高10-HCPT对H22移植瘤的生长抑制效应,并可增强10-HCPT对肿瘤血管生成的抑制作用,有望成为一种新的靶向抗肿瘤治疗手段.
목적 제비재10-간기희수감(10-HCPT)지질초성미포(10-hydroxycamptothecine-loaded liposome microbubbles,HLM),병연구초성정위복조재약미포대H22이식류적생장억제효응.방법 제비재10-HCPT적지질미포급공백지질미포,건립소서간암H22실체류모형,장하류서수궤분위A、B량대조,매조우분위HLM조、10-HCPT주사액조、공백지질미포조화생리염수대조조,경소서미정맥수입약물혹미포후립즉이치료초성복조류체부위,련속치료7 d.A조소서치료결속후박취류괴칭중.계산억류솔,병작병리절편분석종류미혈관밀도(MVD)변화;종치료당천기,묘회B조소서종류생장곡선,병관찰생존기.결과 HLM조억류솔명현고우기타각조,MVD교기타조저(P<0.05),해조소서생존천수교대조조명현연장(P<0.01),단여10-HCPT주사액조비교차이무통계학의의(P>0.05);공백미포조각검측지표여대조조차이무통계학의의(P>0.05).결론 초성파향파배재약미포가현저제고10-HCPT대H22이식류적생장억제효응,병가증강10-HCPT대종류혈관생성적억제작용,유망성위일충신적파향항종류치료수단.
Objective To prepare lipid-coated ultrasound microbubbles containing 10-HCPT(HLM) and explore the antitumor effects on mice xenografed H22 solid tumor using the technique of ultrasound-mediated HLM destruction. Methods Sixty-four tumor-bearing mice were radomly divided into A and B groups. Each group was divided into four groups again and administered respectively by tail vein with HI.M, non-drug-loaded microbubbles,10-HCPT and saline once a day. Ultrasound irradiation was applied on the tumor sites immediately after injection. After 7 days of consecutive treatment, all mice in group A were sacrificed and the tumors were harvested to measure weights. The tumor inhibition rate was calculated by weights. The tumor microvessel density (MVD) was detected by immunohistochemical staining. The tumor growth curve was depicted according to volumes. The survival time of mice in group B was recorded. Results The tumor inhibition rate was the highest in HLM group while this group's MVD was the lowest. Survival time in HLM group and 10-HCPT group were obviously longer compared with the control group,while no statistic difference was observed between the two groups. There was no statistic difference between the group of non-drug-loaded microbubbles and the control group. Conclusions Ultrasound irradiation mediates HLM destruction so that the drug is released from the vihicles at the same time, which can significantly enhance the tumor inhibition effect of 10-HCPT on the H22 tumor. This technique is expected to be adopted as a novel tool for liver cancer chemotherapy.