紫杉醇长循环热敏脂质体对Lewis肺癌移植瘤的抑制作用  

Inhibitory Effect of Paclitaxel Long-circulating Thermo-sensitive Liposome on Lewis Lung Cancer Cells in Mice

作　　者：李美波[1] 顾生玖[1] 赵文鹏[1] 朱开梅[1] 

机构地区：[1]桂林医学院药学院,桂林541004

出　　处：《医药导报》2015年第6期726-729,共4页Herald of Medicine

基　　金：广西科技攻关项目(桂科能129825-21;桂科合14123001-22);广西教育厅项目(201202ZD065;2013YB154);桂林市科技攻关项目(20140105-11;20140122-5;20140105-5;20140105-6;20130103-8;20130103-9;20130113-1;2013l X080)

摘　　要：目的研究紫杉醇长循环热敏脂质体(PLTL)对Lewis肺癌移植瘤的抑制作用。方法建立小鼠Lewis肺癌模型,将40只荷瘤鼠随机分为5组,空白对照组、模型对照组、紫杉醇注射液(PTX)组、紫杉醇热敏脂质体(PTL)组和PLTL组,每组8只。空白对照组和模型对照组注射0.9%氯化钠溶液,PTX组、PTL组和PLTL组,每只小鼠给药总剂量为紫杉醇20 mg·kg-1,采用0.9%氯化钠溶液稀释,每次注射0.2mL。除空白对照组外,其他组给药后5 min内立即将小鼠的肿瘤部位固定于(42±0.5)℃的恒温水浴中加热30 min。治疗期间观察移植瘤体生长情况,苏木精-伊红(HE)染色检测肿瘤组织的病理学形态改变,观察肿瘤细胞的形态学变化,采用流式细胞术检测肿瘤细胞的凋亡率,考察PLTL联合局部热疗对小鼠肿瘤的抑瘤作用。结果模型对照组、PTX组、PTL组和PLTL组抑瘤率分别为21.81%,48.87%,57.22%和78.87%,肿瘤细胞凋亡率分别为(20.4±4.2)%,(42.7±3.8)%,(54.6±2.9)%和(69.7±5.0)%,肿瘤组织切片HE染色发现,PLTL组肿瘤细胞凋亡与坏死数量明显增多。结论 PLTL与PTX,PTL比较,具有明显的热敏靶向性,与局部热疗相结合显著提高紫杉醇的治疗效果。Objective To observe the effect of paclitaxel long-circulating thermo-sensitive liposome （ PLTL） on inhibiting the growth of transplanting Lewis lung cancer cells in C57BL/ 6 mice. Methods The model of mice carried Lewis lung cancer was established. 40 tumor-bearing mice were divided into five groups randomly： blank control group, model control group, PTX group, PTL group and PLTL group, 8 mice for each group. The blank control group and the model control group were injected with 0. 9% sodium chloride solution. In PTX group, PTL group and PLTL group, the dose of per injection was calculated with the reference of PTX for 20 mg·kg-1 , diluted with 0. 9% sodium chloride solution, and the mice were injected via the tail vein with a volume of 0. 2 mL each time. Except for the blank control group, 5 minutes after administration, the tumors of the other groups were subjected to local hyperthermia at （42±0. 5） ℃ for 30 min. During the treatment period, transplantation tumor growth was observed; pathological morphology changes of tumor tissues and cells were detected by HE stain; apoptosis rate of tumor cells was determined by flow cytometry to investigate the inhibition effect of PLTL combined with local thermal therapy on the tumor. Results The inhibition rate of tumor in model control group, PTX group, PTL group and PLTL group was 21. 81% , 48. 87% , 57. 22% and 78. 87% , respectively. The apoptosis rate of tumor cells was （20. 4 ± 4. 2）% , （42. 7 ± 3. 8）% , （54. 6±2. 9）% and （69. 7±5. 0）% , respectively. Observed by pathology, apoptosis rate and necrosis number of tumor cells in PLTL group were significantly increased. Conclusion Compared with PTX and PTL, PLTL has an evident thermo-sensitive feature and can increase the anticancer effect of paclitaxel remarkably when combined with local hyperthermia.

关 键 词：紫杉醇 脂质体 热敏 长循环 癌 肺 

分 类 号：R979.1[医药卫生—药品]