低剂量地西他滨增强T细胞对宫颈癌细胞杀伤活性研究  

Effect of T cell killing ability on low-dose decitabine treated cervical cancer cells

作　　者：白桦[1] 李祥[2] 聂晶[2] 韩卫东[2] 孟元光[1] 

机构地区：[1]解放军总医院妇产科,北京100853 [2]解放军总医院基础医学所分子生物室,北京100853

出　　处：《解放军医学院学报》2015年第5期497-501,共5页Academic Journal of Chinese PLA Medical School

基　　金：国家自然科学基金项目(81472838;81272867)~~

摘　　要：目的研究低剂量地西他滨是否可增强T细胞对宫颈癌细胞杀伤活性,并探讨其可能的作用机制。方法 CCK-8检测低剂量地西他滨对宫颈癌细胞增殖的影响,流式细胞仪检测低剂量地西他滨处理后宫颈癌细胞凋亡及周期的变化;CCK-8检测T细胞对低剂量地西他滨处理后宫颈癌细胞的杀伤作用,实时定量PCR法检测地西他滨处理后宫颈癌细胞癌/睾丸抗原(cancer testis antigen,CTA)及Fas L的m RNA表达的变化。结果 10 nmol/L地西他滨对宫颈癌细胞增殖、凋亡没有显著影响,100 nmol/L地西他滨一定程度上抑制细胞增殖。10 nmol/L地西他滨虽不直接抑制细胞增长,但使宫颈癌细胞对T细胞的杀伤效应更为敏感,以效靶比为10∶1时最显著。10 nmol/L地西他滨处理后宫颈癌细胞BORIS、NY-ESO-1、MAGE-A1/A3/A4等CTA及Fas L的m RNA水平显著上调(P<0.05)。结论低剂量地西他滨可抑制Hela及Si Ha细胞的生长及存活,增强T细胞对Hela及Si Ha细胞的杀伤能力,是一个潜在的免疫治疗辅助药物。Objective To study the effect of T cell killing ability on low-dose decitabine （DAC） treated cervical cancer cells and explore its possible mechanism.Methods CCK-8 was used to test the proliferation of low-dose DAC treated cervical cancer cells. Flow cytometry assay was used to test the apoptosis and cell cycle of low-dose DAC treated cervical cancer cells. CCK-8 was also used to test T cell killing ability of low-dose DAC treated cervical cancer cells. Real-Time PCR was used to test the expression of BORIS, NYESO-1, MAGEA1, MAGEA3, MAGEA4 and FasL on low-dose DAC treated cervical cancer cells.Results 10 nmol/L of DAC showed no significant difference in the proliferation and apoptosis of cervical cancer cells, while 100 nmol/L of DAC inhibited the proliferation of cervical cancer cells. Though 10 nmol/L of DAC did not inhibit the proliferation of cervical cancer cells directly, it enhanced T cell killing ability to cervical cancer cells most significantly with the efficient targeting ratio of 10∶1. Also 10 nmol/L of DAC showed significant up-regulation in the mRNA expression of CTAs such as BORIS, NYESO-1, MAGEA1, MAGEA3 and MAGEA4, as well as FasL.Conclusion These results suggest that low-dose DAC may work as a potential biological immunotherapy drug to inhibit cell viability and enhance T cell killing ability in cervical cancer cells.

关 键 词：地西他滨 宫颈癌 癌睾丸抗原 免疫治疗 

分 类 号：R737.33[医药卫生—肿瘤]