RGD修饰的葫芦素B纳米脂质载体对乳腺癌荷瘤裸鼠的抑瘤作用

摘要

Objective:To prepare RGD conjugated cucurbitacin B loaded liposome(RGD-CuB-NLC) and observe RGD-CuB-NLC’s anti-cancer effect on the treatment with the cells of breast cancer in vitro and RGD-CuB-NLC’s anti-cancer effect on nude mice of human breast cancer.Method:The liposomes were prepared by thin film hydration method,a single cell suspension liquid of the MCF-7 cells of breast cancer was made according to the cultivation of the adherent cell method,then it was inoculated into 96 hole cell culture plate,the group of RGD-CuB-NLC was designed,the control groups were CuB-NLC,RGD-NLC and the blank group of NLC were designed,the rate of suppression in different condition were calculated.Nude mouse transplantation tumor were established,30 qualified nude mice models of human breast cancer xenograft were randomly divided into 5 groups, each group was 6,the mice of 5 groups were respectively treated by CuB,CuB-NLC,RGD-NLC,RGD-CuB-NLC and 0.9% sodium chloride solution every 24 hours per time,7 times in total.The body weight of nude mice and the weight of the transplanted tumor growth were recorded,and the inhibition rate of tumor growth were calculated. Result:For RGD-CuB-NLC group,the form was the circular,the encapsulation rate>80%,partical size was less than 150 nm,the average particle size was (115.6±2.1)nm,polydispersity index was (0.217±0.033),the electric potential was(-12.31±0.76)mV.The inhibition ratio of different liposome on breast cancer cells in the group of NLC was 0,the group of CuB-NLC was (46.3±2.21)%,the group of RGD-NLC was (55.7±3.22)%, the group of RGD-CuB-NLC was (75.6±5.67)%,the differences were statistically significant(P<0.05). In the inhibition rate of tumor growth,there were statistically significant in 0.9% sodium chloride solution group, CuB group,CuB-NLC group and RGD-NLC group compared with RGD-CuB-NLC group(P<0.05).There were statistically significant in CuB group,CuB-NLC group,RGD-NLC group and RGD-CuB-NLC group compared with 0.9% sodium chloride solution group in the inhibition rate of tumor growth(P<0.05).Conclusion:RGD conjugated cucurbitacin B loaded liposome can restrain the proliferation of breast cancer cells and the growth of tumor.%目的：制备RGD修饰的葫芦素B纳米结构脂质载体（RGD-CuB-NLC），观察RGD-CUB-NLC对乳腺癌细胞的体外抑制作用和对乳腺癌荷瘤裸鼠的抑瘤作用。方法：采用薄膜分散法制备得RGD-CuB-NLC，按照贴壁细胞的培养方法，制成MCF-7乳腺癌单细胞混悬液，接种于96孔培养板，建立RGD-CuB-NLC组，CuB-NLC、RGD-NLC为对照组，另设NLC空白组，计算不同条件的抑制率。建立裸小鼠移植瘤，将合格的30只移植瘤裸小鼠随机分成五组，每组6只。分别尾静脉注射CuB注射液， CuB-NLC，RGD-NLC，RGD-CuB-NLC和0.9%氯化钠溶液，每间隔24 h给药1次，共7次，记录鼠重、瘤体质量并计算抑瘤率。结果：RGD-CuB-NLC：形态为圆形，包封率>80%，粒径<150 nm，平均为（115.6±2.1）nm，多分散系数为（0.217±0.033），电位为（-12.31±0.76）mV。不同脂质体对乳腺癌细胞体外抑制率分别为：NLC组为0，CuB-NLC组为（46.3±2.21）%，RGD-NLC组为（55.7±3.22）%， RGD-CuB-NLC组为（75.6±5.67）%，比较差异有统计学意义（P<0.05）。0.9%氯化钠溶液组、CuB组、CuB-NLC组、RGD-NLC组与RGD-CuB-NLC组抑瘤率比较差异均有统计学意义（P<0.05）；CuB组、CuB-NLC组、RGD-NLC组、RGD-CuB-NLC组与0.9%氯化钠溶液组抑瘤率比较差异均有统计学意义（P<0.05）。结论：RGD修饰的葫芦素B纳米结构脂质载体能够抑制乳腺癌细胞的增值和肿瘤的生长。