自然杀伤细胞抑制肝癌肺转移  

Natural killer cells inhibit pulmonary metastasis of hepatocellular carcinoma

作　　者：申九妹[1] 熊共鹏[2] 郑启忠[1] 张宏斌[2] 洪再发[2] 

机构地区：[1]厦门市中医院病理科,福建省厦门市361009 [2]厦门市中医院肝病中心肝外科,福建省厦门市361009

出　　处：《世界华人消化杂志》2017年第22期2028-2038,共11页World Chinese Journal of Digestology

基　　金：福建省科技计划项目青年创新基金资助项目;No.2016D23;福建中医药大学校管课题资助项目;No.XB2015039~~

摘　　要：目的研究自然杀伤(natural killer,NK)细胞对肝癌的抑制作用,为临床应用提供实验依据.方法从人外周血分离培养及鉴定NK细胞.在体外,研究NK细胞抑制肝癌细胞的增殖、迁徙、转移.在体内,检测NK细胞在裸鼠肝脏存活情况.利用人肝癌组织裸鼠肝脏原位移植模型来评估NK细胞在体内对肝癌生长、转移的抑制功能.通过检测NK细胞活化受体、NKB1、穿孔素和颗粒酶的表达情况来评估白介素(interleukin,IL)-2对NK细胞免疫功能的刺激作用.结果采用密度梯度法可以获取较大量的外周血单个核细胞,且能够从中分离到高活力的NK细胞.NK细胞经IL-2激活后活力增高,成簇悬浮繁殖、扩增、生长.在体外,NK细胞可抑制肝癌细胞的增殖、迁移和侵袭.在体内,NK细胞在裸鼠肝脏可长期存活;NK细胞可明显抑制裸鼠肝癌肺转移.然而,NK细胞对肝脏肿瘤生长抑制不明显.IL-2可诱导NK细胞免疫相关分子的表达并提高其肿瘤抑制功能.结论NK细胞的免疫学功能可被IL-2活化从而抑制肝癌的转移.AIM To investigate the inhibitory role of natural killer（NK） cells in liver cancer metastasis.METHODS NK cells were isolated from human peripheral blood mononuclear cells, cultivated and identified. In vitro, NK cells were used to suppress liver cancer cell proliferation,migration and metastasis. In vivo, the homing of NK cells in the liver of nude mice was detected. A nude mouse orthotopic liver transplantation model was used to assess the role of NK cells in inhibiting the growth and metastasis of liver cancer in vivo. The expression of NKG2 D, NKB1, perforin and granular enzyme was detected to assess the stimulatory effect of interleukin（IL）-2 on NK cell immune function.RESULTS In vitro, NK cells inhibited the proliferation,migration and invasion of liver cancer cells. In vivo, NK cells could survive in the liver of nude mice for a long time. NK cells significantly inhibit the pulmonary metastasis of liver cancer in nude mice. However, the liver tumor growth was notinhibited by NK cells. IL-2 can strengthen the suppressor function of NK cells in tumors.CONCLUSION The immunological function of NK cells can be strengthened by IL-2 to inhibit liver cancer metastasis.

关 键 词：自然杀伤细胞 侵袭 肝细胞肝癌 肺转移 白介素-2 

分 类 号：R735.7[医药卫生—肿瘤]