Effect of olanzapine on the proliferation and differentiation of breast cancer-associated macrophages
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-β and IL-10 in the co-culture 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 co-culture 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.
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