摘要
目的探讨奥氮平对乳腺癌细胞共培养体系中人急性髓系白血病细胞系THP-1细胞增殖和分化功能的影响。方法体外培养THP-1细胞、人乳腺癌MDA-MB-231细胞,建立THP-1与MDA-MB-231共培养组,用CCK-8法检测奥氮平处理后的THP-1单独组、共培养组中THP-1的活性变化;用qRT-PCR法检测奥氮平对佛波酯诱导的THP-1单独组、共培养组中THP-1表面分子CD68、CD80、CD163的表达,以及炎症因子IL-1β、IL-6、IL-12、TGF-α、TGF-β和IL-10的表达,同时进一步检测巨噬细胞极化相关miRNA分子miRNA9、miRNA155和miRNA34a的表达。结果奥氮平能抑制THP-1单独组和共培养组中THP-1的增殖活性(P<0.05);在佛波酯诱导THP-1向巨噬细胞分化的研究中,奥氮平能够显著提高THP-1单独组CD68分子的表达(P<0.05),而在共培养组中CD68、CD80、CD163的表达则均显著升高(P<0.05)。在THP-1单独组中,奥氮平仅能够促进IL-12的表达;在共培养组中,奥氮平使CCL2、CXCL10、IL-1β、IL-10、IL-6、IL-12、TNF-α表达水平显著升高(P<0.05)。在巨噬细胞分化相关miRNA的研究中,在奥氮平作用下,THP-1单独组中miR155和Let7c的表达显著升高(P<0.05),miR146、miR9和miR34a的表达变化无差异;在与MDA-MB-231共培养条件下,miR34a和Let7c显著升高(P<0.05)。结论在肿瘤细胞存在的情况下,奥氮平可参与肿瘤相关巨噬细胞表面分子、炎症因子以及巨噬细胞极化相关miRNA分子表达的调节,这为进一步利用奥氮平治疗乳腺癌提供了新思路。
Objective To observe the effect of olanzapine on the proliferation and differentiation of human monocytic leukemia cells(THP-1)in the co-culture system.Methods THP-1 cells and human triple-negative breast cancer cells(MDA-MB-231)were cultured in vitro.A co-culture group of THP-1 and MDA-MB-231 was established.The changes in the activity of THP-1 in the THP-1-alone group and the co-culture group after the treatment with different concentrations of olanzapine were detected by the CCK-8 assay,respectively.Olanzapine on the phorbol myristate acetate-induced THP-1-alone group was detected by qRT-PCR assay.Expressions of THP-1 surface molecules CD68,CD80,and CD163,and inflammatory factors IL-1β,IL-6,IL-12,TGF-α,TGF-βand IL-10 in the coculture group were also detected by qRT-PCR.The expression of macrophage polarization-associated miRNA molecules miRNA9,miRNA155 and miRNA34a were further detected.Results Olanzapine inhibited the proliferation of THP-1 in both THP-1-alone and co-culture groups(P<0.05).In the study of PMA-induced THP-1 differentiation to macrophages,olanzapine significantly increased the expression of CD68 molecules in THP-1-alone group(P<0.05),while in the co-culture group the expression of CD68,CD80 and CD163 were all significantly increased(P<0.05).Further studies showed that in the THP-1-alone group,olanzapine only promoted the expression of IL-12.In the coculture group,olanzapine significantly increased the expression levels of CCL2,CXCL10,IL-1β,IL-10,IL-6,IL-12,and TNF-α(P<0.05).In the study of macrophage differentiation-associated miRNAs,olanzapine significantly increased on the expression of miR155 and Let7c in the THP-1-alone group(P<0.05),and the effect on miR146,miR9 and miR34a was not obvious.In the co-culture with MDA-MB-231,expression of miR34a and Let7c,on the other hand,significantly increased(P<0.05).Conclusion In the presence of tumour cells,olanzapine can regulate the expression of tumour-associated macrophage surface molecules,inflammatory factors,and macrophage polarization-associated miRNA molecules,which may provide new ideas for further use of olanzapine in the clinical treatment of breast cancer.
作者
孟娟
李东辉
高元慧
刘梅
李建旺
MENG Juan;LI Dong-hui;GAO Yuan-hui;LIU Mei;LI Jian-wang(Department of Oncology,Haikou Municipal Hospital,HaiKou 570208;Department of Urology,Haikou Municipal Hospital,HaiKou 570208;Department of Central Laboratory,Haikou Municipal Hospital,HaiKou 570208)
出处
《中南药学》
CAS
2024年第2期341-346,共6页
Central South Pharmacy
基金
海南省卫生健康行业科研项目(No.22A200121,No.20A200358)。
关键词
奥氮平
乳腺癌
急性髓系白血病THP-1细胞
增殖
分化
olanzapine
breast cancer
acute myeloid leukemia THP-1 cell
proliferation
differentiation
