DC-CTL免疫细胞对卵巢上皮癌细胞的靶向性治疗研究

Targeted therapy of ovarian epithelial cancer by DC-CTL immune cells

目的探讨经树突状细胞(DC)诱导的细胞毒性T淋巴细胞(CTL)免疫细胞靶向性的抑制卵巢上皮癌细胞的机制,为临床上DC-CTL治疗卵巢癌提供理论基础。方法无胸腺BALB/C/nu/nu裸小鼠48只,分为4组,每组12只,裸鼠人卵巢癌SKOV3移植瘤模型成功后用未经DC诱导的CTL免疫细胞和经DC诱导的CTL免疫细胞进行治疗,比较各组裸鼠移植瘤体积和重量、抑瘤率、移植瘤miRNAlet-7表达和HMGA2蛋白表达的差异。结果 DC-CTL组和CTL组裸鼠的移植瘤体积和移植瘤重量低于模型对照组(F值分别为8.175、6.823,均P<0.05),DC-CTL组裸鼠的移植瘤体积和移植瘤重量低于CTL组,且差异具有统计学意义(t=13.244,P<0.05);DC-CTL组裸鼠的抑瘤率(69.57±10.81)%高于CTL组(42.35±8.15)%,且差异具有统计学意义(t=6.965,P<0.05);DC-CTL组和CTL组裸鼠的移植瘤miRNAlet-7表达均高于模型对照组(F=7.528,P<0.05),DC-CTL组裸鼠的移植瘤miRNAlet-7表达(1.69±0.40)高于CTL组(1.17±0.39),且差异具有统计学意义(t=2.964,P<0.05);DC-CTL组和CTL组裸鼠的HM GA2蛋白表达的ISH评分均低于模型对照组(F=6.419,P<0.05),DC-CTL组裸鼠的HM GA2蛋白表达的ISH评分(15.31±1.72)低于CTL组(17.18±1.86),且差异具有统计学意义(t=3.143,P<0.05)。结论经DC诱导的CTL免疫细胞能够明显抑制裸鼠卵巢癌移植瘤的生长,其机制可能为促进let-7表达和抑制HMGA2蛋白表达有关。

Objective To investigate the mechanism of targeted inhibiting epithelial ovarian cancer （ EOC ） by cytotoxic T lymphocyte （ CTL） immune cells induced by dendritic cell （ DC） so as to provide theoretical basis for clinical treatment of ovarian cancer by DC -CTL. Methods Forty-eight BALB/C/nu/nu nude mice were divided into 4 groups with 12 in each group.After SKOV3 ovarian cancer cells transplanted tumor model was successful , nude mice were treated with CTL immune cells without DC induction and DC induced CTL immune cells.Comparison was made among different groups in volume and weight of transplanted tumor , tumor inhibition rate, miRNAlet-7 expression and HMGA2 protein expression.Results The tumor volume and weight of transplanted tumor in DC-CTL group and CTL group were lower than those in model group （F value was 8.175 and 6.823, respectively, both P〈0.05）.Those in DC-CTL group were lower than those in CTL group with statistical differences （t=13.244, P〈0.05）.The tumor inhibition rate （69.57 ±10.81%） in DC-CTL group was higher than that in CTL group （42.35 ±8.15%）, and the difference was statistically significant （t=6.965, P〈0.05）.The expression of miRNAlet-7 in DC-CTL group and CTL group was higher than that in model group （F=7.528, P〈0.05）, and that in CTL group （1.69 ±0.40） was significantly higher than that in DC-CTL group （1.17 ±0.39） with significant difference （t =2.964, P〈0.05）.The ISH score of HMGA2 protein expression in DC-CTL group and CTL group was lower than that in model group （F=6.419, P〈0.05）, and that in DC-CTL group （15.31 ±1.72） was lower than that in CTL group （17.18 ±1.86） with significant difference （t=3.143, P〈0.05）.Conclusion CTL immune cells induced by DC can significantly inhibit the growth of ovarian cancer transplanted tumor in nude mice , and the mechanism may be related to the promotion of let-7 expression and inhibition of HMGA 2 protein expression .