DC-CTL免疫细胞对卵巢上皮癌细胞的靶向性治疗研究

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HMGA2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HMGA2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。

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

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 .