CD105对绒毛膜癌裸鼠移植瘤生长及耐药性的影响

Effect of CD105 on growth and chemoresistance of choriocarcinoma xenografts in nude mice

目的:探讨绒毛膜癌裸鼠移植瘤模型中的成瘤情况,以及CD105及相关蛋白在移植瘤中表达水平与化疗耐药的相关性。方法:将90只健康BALB/c裸鼠随机分为3组JEG-3细胞(野生型)、JEG-3/CD105 OE(过表达型)与JEG-3/shCD105(敲减表达型),每组30只,建立CD105表达相关的绒癌裸鼠移植瘤模型。甲氨蝶呤单药化疗5天后,比较野生型、过表达型和敲减表达型中各化疗组和对照组移植瘤的质量及体积,并计算抑瘤率。Western blot法和免疫荧光法检测各组裸鼠移植瘤中CD105、BMP9及Smads蛋白水平,ELISA法检测各组裸鼠血清中CD105的水平。结果:各型移植瘤成瘤率均为100%。野生型移植瘤的生长速度均慢于过表达型而快于敲减表达型,差异有统计学意义(P<0.05)。野生型、过表达型、敲减表达型移植瘤的生长抑制率分别为(42.23±2.33)%、(31.03±5.76)%和(56.00±3.15)%;过表达型移植瘤对化疗的耐药性高于野生型、敲减表达型移植瘤,差异有统计学意义(P<0.05)。野生型移植瘤中CD105、BMP9表达水平均低于过表达型而高于敲减表达型,差异有统计学意义(P<0.05)。野生型、过表达型、敲减表达型移植瘤裸鼠血清中CD105浓度分别为(3356.27±453.19)pg/mL、(3661.90±471.09)pg/mL和(3226.91±471.10)pg/mL,过表达型裸鼠血清CD105浓度高于野生型和敲减表达型,差异有统计学意义(P<0.05)。结论:在裸鼠移植瘤模型中证明了移植瘤体中CD105、BMP9表达水平、血清中CD105表达水平与移植瘤的耐药程度具有一致性,为后续绒癌裸鼠移植瘤的耐药性机制研究奠定了基础。

Objective:To investigate the tumorigenesis of choriocarcinoma in nude mice and the correlation between the expressions of CD105 and CD105 related proteins and chemoresistance.Methods:Ninety healthy BALB/C nude mice were randomly divided into three groups:JEG-3 cells(wild type)and JEG-3/CD105 OE(overexpression type)and JEG-3/shCD105(knockdown type)were used to establish CD105 expression related choriocarcinoma xenograft model in nude mice.After 5 days of methotrexate monotherapy,the mass and volume of transplanted tumor in the wild-type,overexpression and knockdown expression groups were compared with those in the control group,and the tumor inhibition rate was calculated.The levels of CD105,BMP9 and Smads protein in nude mice were detected by blot and immunofluorescence,and the levels of CD105 in serum were detected by ELISA.Results:The growth rate of wild-type transplanted tumor was slower than that of overexpression type and faster than that of knockdown expression type(P<0.05).The growth inhibition rate of wild-type transplanted tumor was(42.23±2.33)%,the growth inhibition rate of overexpression transplanted tumor was(31.03±5.76)%,and the growth inhibition rate of knockdown expression transplanted tumor was(56.00±3.15)%.The expression levels of CD105 and BMP9 in wild-type xenografts were lower than those in overexpression type and higher than those in knockdown type(P<0.05).The concentration of CD105 in serum of wild-type nude mice was(3356.27±453.19)pg/mL,and that of overexpression nude mice was(3661.90±471.09)pg/ml,that of knockdown nude mice was(3226.91±471.10)pg/mL.The concentration of CD105 in serum of overexpression nude mice was higher than that of wild-type and knockdown nude mice,and the difference was statistically significant(P<0.05).Conclusion:The expression level of CD105 and BMP9 in xenografts and the expression level of CD105 in serum were consistent with the degree of drug resistance of xenografts,which laid a foundation for the follow-up study of drug resistance mechanism of choriocarcinoma xenografts in nude mice.