[SERPINE1 overexpression promotes proliferation and paclitaxel resistance of triple-negative breast cancer cells by inducing M2 macrophage polarization].

OBJECTIVES: To investigate the regulatory effect of Serpin Family E Member 1 (SERPINE1) on immune microenvironment and paclitaxel (PTX) resistance of triple-negative breast cancer (TNBC) cells. METHODS: CCK-8 assay was used to determine the half-maximal inhibitory concentration of PTX in TNBC cell line MDA-MB-231. In wild-type MDA-MB-231 cells and a PTX-resistant MDA-MB-231 cell line (MDA-MB-231/PTX) established by stepwise increasing low-dose PTX treatment, the effects of Western blot-verified transfection with SERPINE1 overexpression plasmids or SERPINE1 siRNAs on cell apoptosis were evaluated using Hoechst 33258 staining and by detecting expression levels of cleaved caspase-3 using Western blotting. The changes in proliferation of the transfected cells were assessed using EdU and CCK-8 assays. The breast cancer cells with different treatments were co-cultured with macrophages, and M1 and M2 polarization of the macrophages were analyzed with flow cytometry and Western blotting. In nude mouse models bearing subcutaneous breast cancer cell xenografts, the effects of SERPINE1 overexpression and knockdown in the engrafted cells on tumor growth and PTX resistance were evaluated. RESULTS: SERPINE1 overexpression significantly inhibited apoptosis and promoted proliferation of MDA-MB-231 cells, and SERPINE1 knockdown obviously promoted apoptosis and inhibited proliferation of MDA-MB-231/PTX cells. The macrophages co-cultured with SERPINE1-overexpressing breast cancer cells showed enhanced M2 polarization and suppressed M1 polarization with a lowered M1/M2 ratio. In the tumor-bearing nude mouse models, SERPINE1 overexpression in the engrafted cells resulted in significantly accelerated tumor growth. CONCLUSIONS: In MDA-MB-231 cells, SERPINE1 overexpression promotes cell proliferation, inhibits apoptosis, and enhances PTX resistance. SERPINE1 plays a regulatory role in macrophage polarization in the immune microenvironment of breast cancer, and its high expression promotes M2 polarization of the macrophages.