亚高温场中载水飞蓟宾热敏脂质体—微泡复合体对兔肝VX_2肿瘤的作用研究
|
摘要
目的观察在亚高温场中载水飞蓟宾热敏脂质体——微泡复合体(STLMC)对兔肝VX2肿瘤的作用。方法将40只VX2荷瘤兔的40个肝转移瘤随机分为4组,每组10只动物:微波亚高温辐照组(SHM)、水飞蓟宾载药微泡组(STLMC)、微波亚高温辐照联合水飞蓟宾载药微泡治疗组(SHM+STLMC)、空白对照组(BL)。分别给予不同干预:微波热辐照、STLMC注射、微波热辐照联合STLMC注射、无辐照无注射。治疗后7d及21d,采用二维灰阶超声、超声造影成像分别评价术后各组肿瘤体积和最大径的变化。透射电镜观察各组干预区超微结构变化。结果 SHM+STLMC组术后7d及21d肿瘤体积及最大径均明显小于同期其余各组(P<0.05);电镜下各组均出现染色质异常、细胞器受损的巨噬细胞,SHM+STLMC组受损巨噬细胞数目较其余各组明显增多(P<0.05)。结论在亚高温场中STLMC可造成肿瘤微环境中巨噬细胞形态破坏,抑制肿瘤生长。
Objective To observe the effects of silibinin-loaded temperature sensitive liposome-microbubble complex(STLMC)on rabbit VX2 tumor in the sub-hyperthermia field.Methods 40 rabbits with VX2 liver tumors were randomly divided into 4groups(10animals in each group):sub-hyperthermia microwave group(SHM),silibininloaded temperature sensitive liposome-microbubble complex group(STLMC),sub-hyperthermia microwave plus silibinin-loaded temperature sensitive liposome-microbubble group(SHM+STLMC),blank control group(BL).These groups underwent different treatment methods respectively:microwave ablation,STLMC injection,microwave ablation combined with STLMC injection and no treatment.Five rabbits in each group were examined by using 2DUS and contrast-enhanced ultrasound imaging to evaluate changes of the tumor volume and maximum diameter before treatment and on 7d,21 dafter treatment.And then the rabbits were sacrificed and the ultramicrostructure in tumor tissues were observed under transmission electron microscope.Results After 7dand 21 d,the post-treatment volume and the maximum diameter of the tumors in group SHM+STLMC were smaller than the other group(P<0.05).Under electron microscope,it was demonstrated in each group that the chromatins showed abnormal and cell organelles were destroyed in some of macrophages.Especially,in the SHM + STLMC group,the number of damaged macrophages were obviously increased than the other group(P<0.05).Conclusions STLMC had the potential role to prevent the tumor growth,possibly by inhibiting macrophages in tumor microenvironment.
Objective To observe the effects of silibinin-loaded temperature sensitive liposome-microbubble complex(STLMC)on rabbit VX2 tumor in the sub-hyperthermia field.Methods 40 rabbits with VX2 liver tumors were randomly divided into 4groups(10animals in each group):sub-hyperthermia microwave group(SHM),silibininloaded temperature sensitive liposome-microbubble complex group(STLMC),sub-hyperthermia microwave plus silibinin-loaded temperature sensitive liposome-microbubble group(SHM+STLMC),blank control group(BL).These groups underwent different treatment methods respectively:microwave ablation,STLMC injection,microwave ablation combined with STLMC injection and no treatment.Five rabbits in each group were examined by using 2DUS and contrast-enhanced ultrasound imaging to evaluate changes of the tumor volume and maximum diameter before treatment and on 7d,21 dafter treatment.And then the rabbits were sacrificed and the ultramicrostructure in tumor tissues were observed under transmission electron microscope.Results After 7dand 21 d,the post-treatment volume and the maximum diameter of the tumors in group SHM+STLMC were smaller than the other group(P<0.05).Under electron microscope,it was demonstrated in each group that the chromatins showed abnormal and cell organelles were destroyed in some of macrophages.Especially,in the SHM + STLMC group,the number of damaged macrophages were obviously increased than the other group(P<0.05).Conclusions STLMC had the potential role to prevent the tumor growth,possibly by inhibiting macrophages in tumor microenvironment.
引文
[1]Ahmed M,Goldberg SN.Basic science research in thermal ablation.Surg Oncol Clin N Am,2011,20:237-258.
[2]李欣,董宝玮.超声新技术在局部热消融治疗肝肿瘤中的研究进展.中国超声医学杂志,2011,27(9):855-857.
[3]Kim JH,Kim K,Jin HM,et al.Silibinin inhibits osteoclast differentiation mediated by TNF family members.ol Cells,2009,28:201-207.
[4]Cheung CW,Gibbons N,Johnson DW,et al.Silibinin--apromising new treatment for cancer.Anticancer Agents Med Chem,2010,10:186-195.
[5]李端,罗文,张云飞,等.新型载水飞蓟宾热敏脂质体-微泡Sono Vue复合体制备及质量分析.中国超声医学杂志,2015,31(3):250-253.
[6]Luo W,Zhou X,Yu M,et al.Ablation of high-intensity focused ultrasound assisted with SonoVue on Rabbit VX2liver tumors:sequential findings with histopathology,immunohistochemistry,and enzyme histochemistry.Ann Surg Oncol,2009,16(8):2359-2368.
[7]郭靓,钱露,郭宁.炎症——肿瘤恶性演进的推手.中国肿瘤生物治疗杂志,2013,(3):259-265.
[8]李晓曦,郭宁,曹雪涛.肿瘤相关巨噬细胞促进肿瘤生长与转移的研究现状.中国肿瘤生物治疗杂志,2008,15(1):788-781.
[9]董桂芳,冉海涛,王志刚,等.低强度聚焦超声联合载药微泡靶向治疗兔VX2肿瘤的实验研究.中国超声医学杂志,2013,29(9):836-839.
[10]Tyagi A,Singh RP,Ramasamy K,et al.Growth inhibition and regression of lung tumors by silibinin:modulation of angiogenesis by macrophage-associated cytokines and nuclear factor-kappaB and signal transducers and activators of transcription 3.Cancer Prev Res(Phila),2009,2(1):74-83.
[2]李欣,董宝玮.超声新技术在局部热消融治疗肝肿瘤中的研究进展.中国超声医学杂志,2011,27(9):855-857.
[3]Kim JH,Kim K,Jin HM,et al.Silibinin inhibits osteoclast differentiation mediated by TNF family members.ol Cells,2009,28:201-207.
[4]Cheung CW,Gibbons N,Johnson DW,et al.Silibinin--apromising new treatment for cancer.Anticancer Agents Med Chem,2010,10:186-195.
[5]李端,罗文,张云飞,等.新型载水飞蓟宾热敏脂质体-微泡Sono Vue复合体制备及质量分析.中国超声医学杂志,2015,31(3):250-253.
[6]Luo W,Zhou X,Yu M,et al.Ablation of high-intensity focused ultrasound assisted with SonoVue on Rabbit VX2liver tumors:sequential findings with histopathology,immunohistochemistry,and enzyme histochemistry.Ann Surg Oncol,2009,16(8):2359-2368.
[7]郭靓,钱露,郭宁.炎症——肿瘤恶性演进的推手.中国肿瘤生物治疗杂志,2013,(3):259-265.
[8]李晓曦,郭宁,曹雪涛.肿瘤相关巨噬细胞促进肿瘤生长与转移的研究现状.中国肿瘤生物治疗杂志,2008,15(1):788-781.
[9]董桂芳,冉海涛,王志刚,等.低强度聚焦超声联合载药微泡靶向治疗兔VX2肿瘤的实验研究.中国超声医学杂志,2013,29(9):836-839.
[10]Tyagi A,Singh RP,Ramasamy K,et al.Growth inhibition and regression of lung tumors by silibinin:modulation of angiogenesis by macrophage-associated cytokines and nuclear factor-kappaB and signal transducers and activators of transcription 3.Cancer Prev Res(Phila),2009,2(1):74-83.