悬浮培养肿瘤细胞的生物钟同步化细胞模型建立及其在择时给药研究中的应用

(1.厦门大学附属中山医院肿瘤放疗科,福建 厦门 361004; 2.福州大学生命科学研究所,福建 福州 350116; 3.福建医科大学附属协和医院放疗科,福建 福州 35001; 4.深圳大学医学部,卡尔森国际肿瘤中心,广东 深圳 518060)

生物钟; 肿瘤治疗; 同步化; 药物反应; 细胞培养

Biological clock synchronization of cancer cells based on suspension culture and its application in the study of time administration
QIN Wenjuan1,PAN Meiping2,SU Zejie2,HOU Rurong1,LU Haijie1,3*,YUE Zhicao4*

(1.Department of Radiation Oncology,Zhongshan Hospital of Xiamen University,Xiamen 361004,China; 2.Institute of Life Sciences,Fuzhou University,Fuzhou 350116,China; 3.Department of Radiation Oncology,The Affiliated Union Hospital of Fujian Medical Univers

DOI: 10.6043/j.issn.0438-0479.201912018

备注

生物钟与肿瘤的发生和治疗都密切相关,但目前体外培养的肿瘤细胞同步化方法欠佳,导致体外培养的肿瘤细胞很难表现出生物钟节律现象.针对上述问题,采用悬浮培养的方法,同时进行同步化处理,定时取样分析,在体外细胞培养体系中可获得良好的周期性生物钟节律.将该同步化培养方法用于不同的生物钟节律阶段给药,能引起肿瘤细胞的差异反应,即择时给药的效果.该研究提供了一种可以在体外细胞培养体系中广泛采用的生物钟同步化新方案,可用于探讨生物钟调控肿瘤细胞药物反应的机制.
Biological clock is intricately linked with tumor formation and its treatment.However,cancer cells cultured in vitro showed weak biological clock rhythm due to lack of good method to synchronize their clock.Here we developed a new method to deal with this problem.Cancer cells were cultured in suspension and synchronized,and sampled at designated time points for analysis.Well defined biological clock rhythm was achieved with this method.We then demonstrated that following the above treatment protocol,drugs were able to induce different responses at different biological clock rhythmic stages,exhibiting the circadian clock response.Thus,this method supplies a new strategy for biological clock synchronization of in vitro cultured cells,which can be widely applied to characterize the mechanism of how biological clock regulates chemotherapy responses in cell culture.