紫杉醇长循环热敏脂质体对Lewis肺癌荷瘤鼠的药效学

目的:考察紫杉醇长循环热敏脂质体(PLTL)对Lewis肺癌荷瘤小鼠的药效学。方法:构建Lewis肺癌荷瘤肿瘤模型,随机分为5组:对照组、加热组、紫杉醇注射液(PTX)组、紫杉醇普通热敏脂质体(PTL)组和PLTL组。治疗期间观察小鼠生活状态,检测瘤重抑瘤率;将肿瘤组织切片进行HE染色,观察细胞形态学变化;采用流式细胞仪和TUNEL法检测肿瘤细胞的凋亡率;分析荷瘤小鼠生存状况,绘制荷瘤小鼠生存曲线。结果:PTX、PTL组和PLTL组的瘤重抑廇率分别为46.15%、51.48%和70.12%,流式细胞术和TUNEL法显示PTX、PTL和PLTL均可明显抑制荷瘤小鼠肿瘤生长,且凋亡率逐渐增强;肿瘤组织切片HE染色发现,PLTL可明显抑制肿瘤生长,并在肿瘤局部产生炎症反应;生存实验分析显示PLTL可减小紫杉醇的毒副作用,延长小鼠生存期。结论:PLTL与PTX和PTL相比,PLTL具有明显的热敏靶向性,PLTL与局部热疗相结合可显著增强紫杉醇的抗癌活性。

Pharmacodynamics of paclitaxel long-circulating thermo-sensitive liposome in Lewis tumor-bearing mice

OBJECTIVE To investigate the tumor inhibiting effects of paclitaxel long-circulating thermo-sensitive liposome(PLTL) in mice bearing Lewis lung carcinoma cells.METHODS A tumor-bearing mouse model was established and divided into five groups randomly: control, heat, PTX, paclitaxel thermo-sensitive liposome (PTL) and PLTL groups.The tumor activity of PLTL subject to local hyperthermia was determined by detecting the weight of tumor, observing tumor tissue and its organization form by HE and detecting cell apoptosis by flow cytometry and TUNEL. RESULTS The inhibition ratio of tumor in PTX, PTL and PLTL groups was 46.15%, 51.48% and 70.12%, respectively. Cell apoptosis was detected by flow cytometric and TUNEL method, PTX, PTL and PLTL could induce tumor cell apoptosis and to achieve tumor inhibition, the apoptosis rates: PLTL > PTL > PTX. As observed by pathology, PLTL could increase anticancer effects and cause local inflammation response. Survival experiments showed that, PLTL could reduce drug side effects and prolong the survival time. CONCLUSION Compared with PTX and PTL, PLTL has evident thermo-sensitive characteristics and can enhance the antitumor activity of paclitaxel remarkably when combined with local hyperthermia.