紫杉醇对IL-36γ介导的抗肿瘤作用的影响  

The influence of paclitaxel on IL-36γ-mediated tumor suppression

作　　者：鲁翰林 宋盈莹 申春苹 陈晨 刘小草 冯超 卢斌峰[1] 朱一蓓[1] 孙中文[3] 王雪峰[1] LU Han-lin;SONG Ying-ying;SHEN Chun-ping;CHEN Chen;LIU Xiao-cao;FENG Chao;LU Bin-feng;ZHU Yi-bei;SUN Zhong-wen;WANG Xue-feng(School of Biology and Basic Medical Sciences,Soochow University,Suzhou Jiangsu 215123;School of Medicine and Technology,Suzhou Vocational Health College,Suzhou Jiangsu 215009;Institutes for Translational Medicine,Soochow University,Suzhou Jiangsu 215123,China)

机构地区：[1]苏州大学基础医学与生物科学学院,江苏苏州215123 [2]苏州大学转化医学研究院,江苏苏州215123 [3]苏州卫生职业技术学院医学技术学院,江苏苏州215009

出　　处：《江苏大学学报（医学版）》2018年第5期381-385,共5页Journal of Jiangsu University：Medicine Edition

基　　金：国家自然科学基金资助项目(91642103;31570889;31670916);江苏省六大人才高峰高层次人才资助项目(SWYY-065);江苏省卫计委职业教育研究课题(J201701)

摘　　要：目的:探讨不同剂量紫杉醇对IL-36γ介导的抗肿瘤作用的影响。方法:构建重组表达载体p CDEF3-IL-36γ,再经基因转染、亚克隆筛选和实时定量PCR(RT-q PCR)鉴定,构建可稳定表达IL-36γ的转染细胞株B16-IL-36γ;利用荷瘤小鼠模型,观察转染表达的IL-36γ对肿瘤生长的影响;将肿瘤细胞转染表达的IL-36γ联合不同剂量紫杉醇(0,12.5,25和100μg)进行C57BL/6J雌鼠腹腔注射,分析紫杉醇对肿瘤直径的影响,并检测肿瘤中干扰素-γmRNA的表达。结果:成功获得能稳定表达IL-36γ的转染细胞株B16-IL-36γ;IL-36γ可显著抑制B16肿瘤的生长;100μg剂量的紫杉醇明显抑制了IL-36γ介导的抑肿瘤生长作用和肿瘤中干扰素-γ表达,而12.5μg剂量的紫杉醇则对IL-36γ介导的抑肿瘤生长和肿瘤中干扰素-γ表达具有促进作用。结论:采用IL-36γ进行肿瘤免疫治疗的同时,不宜采用高剂量紫杉醇,但可联合低剂量紫杉醇达到一定的协同效果。Objective： To investigate the influence of paclitaxel on IL36γmediated antitumor effect at different doses. Methods： The transfect B16IL36γ, which can stably secret IL36γ protein,was established by transfecting the recombinant expression vector pCDEF3IL36γ into B16 cell line,selecting with G418, subcloning and validating using RTqPCR method.At the same time, the control B16vec was obtained.The characteristics of tumor expressedIL36γmediated tumor growth suppression was analyzed by constructing mouse tumor model with B16IL36γ as well as B16vec. The influence of paclitaxel on IL36γ mediatedtumor arrest was investigated through observing tumor growth and measuring the level of interferonγ（IFNγ） mRNA expression in tumors after paclitaxel was inoculated intraperitoneally at different doses（0,12.5,25 and 100 μg）. Results： The transfected cell line B16IL36γ, which stably expressed IL36γ, was successfully obtained. Our findings showed that IL36γ could significantly inhibit the growth of B16 tumors.A higher dose of paclitaxel with 100 μg could significantly suppress IL36γmediated inhibition of tumor growth and IFNγ expression in tumor tissue.However,a lower dose of paclitaxel with 12.5 μg exerted a synergistic effect on inhibition of tumor growth and IFNγ mRNA expression. Conclusion： Lower dose of paclitaxel may be used to combine with cytokine IL-36γ in tumor immunotherapy for achieving a certain synergistic effect.

关 键 词：IL-36γ 紫杉醇 肿瘤生长 干扰素-Γ 

分 类 号：R392.1[医药卫生—免疫学]