NK-92细胞联合靶向Her2基因的siRNA治疗卵巢癌的体外及动物实验

    Experiment of NK-92 cells combined with siRNA targeting Her2 gene in the treatment of ovarian cancer in vivo and in vitro

    • 摘要: 目的:探讨NK-92细胞对抑制Her2基因表达的卵巢癌细胞株SKOV-3细胞在体外及体内的杀伤活性。方法:靶向Her2的siRNA转染SKOV-3,筛选得到能稳定抑制Her2基因表达的细胞株SKOV-3/siRNA,并通过RT-PCR和免疫组织化学方法检测Her2基因抑制效果。应用LDH法检测NK-92细胞对SKOV-3、SKOV-3/siRNA的杀伤活性。将SKOV-3、SKOV-3/siRNA细胞接种到裸鼠皮下检测荷瘤情况,并比较NK-92细胞在各组治疗效果。结果:建立了稳定抑制Her2基因表达的细胞株SKOV-3/siRNA,Her2基因表达受到较强抑制。NK-92在效靶比1:20时对SKOV-3、SKOV-3/siRNA细胞杀伤率分别为(21.1±6.8)%和(45.5±8.9)%,差异有统计学意义(P<0.01)。接种SKOV-3/siRNA细胞实验组各时间点瘤体积均明显小于SKOV-3对照组(P<0.05~P<0.01)。SKOV3/siRNA+ NK-92治疗组肿瘤质量均小于其他各组(P<0.05~P<0.01)。结论:NK-92细胞联合靶向Her2基因的siRNA可以抑制卵巢癌细胞株SKOV-3在体外和体内增殖,有望成为卵巢肿瘤治疗的新途径。

       

      Abstract: Objective: To explore the inhibition effects of NK-92 cells on the Her-2 gene expression in SKOV-3 cells in vitro and in vivo.Methods: The SKOV-3/siRNA cell line with persistent silencing the Her2 gene expression were established by the siRNA targeting Her2 gene transfecting into SKOV-3 cell line.The inhibition effects on Her2 gene mRNA expression were detected by RT-PCR and immunohistochemistry.The killing activity of NK-92 cells to SKOV-3 and SKOV-3/siRNA was detected by LDH.The tumor growth in the nude mice inoculated with SKOV-3 and SKOV-3/siRNA subcutaneously was observed.The effects of NK-92 cells on ovarian cancer in all cases were compared.Results: The SKOV-3/siRNA cell line with persistent silencing the Her2 gene expression was established,the Her2 gene expression was strong inhibited.The killing rates of NK-92 cells to SKOV-3 and SKOV-3/siRNA were(21.1±6.8)% and(45.5±8.9)% at 1:20 of the target ratio,respectively(P<0.01).The tumor volume in mice inoculated with SKOV-3/siRN cells was significantly less than that in mice inoculated with ASKOV-3(P<0.05 to P<0.01),The tumor quality in mice treated with SKOV-3/siRN combined with NK-92 cells were significantly less than that in other mice(P<0.05 to P<0.01).Conclusions: NK-92 cells combined with siRNA targeting Her2 gene can inhibit the proliferation of the ovarian cancer cell line SKOV-3 in vitro and in vivo,which may become a new approach of ovarian cancer therapy.

       

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