靶向治疗下乳腺癌干细胞发生发展动力学分析  

Dynamic analysis of breast cancer stem cells growth under targeted therapy

作　　者：宗如月 罗新鹏 李雅倩 赵同军 ZONG Ruyue;LUO Xinpeng;LI Yaqian;ZHAO Tongjun(Institute of Biophysics,School of Science,Hebei University of Technology,Tianjin 300401,China)

机构地区：[1]河北工业大学理学院生物物理研究所,天津300401

出　　处：《河北工业大学学报》2023年第4期24-30,56,共8页Journal of Hebei University of Technology

基　　金：国家自然科学基金(11735006)。

摘　　要：为了研究靶向治疗下乳腺癌干细胞的生长情况,本文在Gompertzian生长模型基础上建立不同状态乳腺癌干细胞理论模型。考虑乳腺癌干细胞的增殖、死亡及特定肿瘤微环境对不同状态乳腺癌干细胞发生发展的影响,用非线性Hill函数描述乳腺癌干细胞对其自身生长速率的反馈,采用解析和数值方法研究不同状态乳腺癌干细胞发生发展。结果表明:在ka(dad0)=1处发生音叉分岔,ka(dad0)<1时无乳腺癌干细胞,ka(dad0)>1时存在乳腺癌干细胞;在乳腺癌干细胞靶向治疗期间,乳腺癌干细胞量急剧降低,并维持一段时间的休眠状态,最后随着疗效减弱,又回到稳定增殖水平;增加活跃状态乳腺癌干细胞的死亡率,可能延长乳腺癌干细胞处于休眠状态的时间。在不同状态的乳腺癌干细胞发生发展过程中,其增殖、死亡及特定肿瘤微环境均起着关键作用。还发现靶向治疗和肿瘤微环境的改变对抑制乳腺癌复发都有一定作用。The growth of breast cancer stem cells is studied under targeted therapy.On the basis of the Gompertzian the⁃oretical growth model,a theoretical model of various states of breast cancer stem cells was established.We considered the influence of breast cancer stem cells’proliferation,death and specific tumor microenvironment on the occurrence and development of breast cancer stem cells in various states.The nonlinear Hill model was also introduced to depict breast cancer stem cells’feedback to its own growth rate.The growth process of breast cancer stem cells in various states was studied by analytical and numerical methods.The results of the study are as follows:a pitchfork bifurcation oc⁃curs at(ka(dad0)=1);This system has no breast cancer stem cells(ka(dad0)<1),on the contrary,this system has breast cancer stem cells;during breast cancer stem cells targeted therapy,the levels of breast cancer stem cells drop sharply,and breast cancer stem cells remain dormant for a period of time;the levels of them rise until they have reached the stage of stable proliferation again with diminished efficacy;the dormancy time of breast cancer stem cells may be prolonged by increasing the mortality of active breast cancer stem cells.Theirs proliferation,death and specific tumor microenviron⁃ment all play key roles in the growth of the dormant and active state of breast cancer stem cells.Also we have found that targeted therapy and the modification of the tumor microenvironment may have some effect on inhibiting breast cancer re⁃currence.

关 键 词：乳腺癌干细胞 靶向治疗 休眠状态 活跃状态 数学建模 

分 类 号：R737.9[医药卫生—肿瘤]