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Psoralen could inhibit the proliferation of human breast cancer cells, however, the molecular mechanism was unclear. We evaluated the anti-proliferative effects of psoralen by MTT, plate colony formation assay and cell cycle analysis in MCF-7 and MDA-MB-231 cells. The effects of psoralen on activation of Wnt/β-catenin and the related target genes were examined by quantitative real-time PCR, western blotting and cell immunofluorescence. The tumor growth was conducted in BALB/c nude mice and the pathological changes of heart, liver and kidney were also observed. Our results demonstrate that psoralen significantly inhibited cell proliferation by inducing G0/G1 phase arrest in MCF-7 cells and G2/M phase arrest in MDA-MB-231 cells. The expression of Fra-1 was reduced and Axin2 was promoted both in MCF-7 and MDA-MB-231 cells after psoralen treatment. The cytoplasmic accumulation and nuclear translocation of β-catenin were significantly reduced by psoralen. Psoralen increased the levels of phospho-(Y142) β-catenin, while decreased the expression of total β-catenin and its downstream target Fra-1 in vitro and vivo. Moreover, psoralen didn’t cause any significant toxicity at the effective concentration. Overall, our results might provide theoretical basis for clinical application of psoralen in breast cancer.

No abstract

Background. Plasma cell mastitis (PCM) is one of the most frequently encountered inflammatory diseases of the nonlactating breast. However, its pathogenesis has remained unknown. Methods. In this study, we observed the ultrastructure changes of PCM by a transmission electron microscope. The transcriptome expression difference of exosomes was detected by RNA-Seq; then, we confirmed the key difference genes by western blot and immunohistochemistry. Finally, we established the mouse PCM model by tissue homogenate injection to validate the role of exosomes on the progression of PCM. Results. The analysis of the exosomal transcriptome expression difference between PCM and normal mammary tissues using RNA-Seq showed the differential genes and enrichment pathways involved in the course of PCM. The decreased HSP90AA1 and EEF2, excessive production of p-AKT, and p-mTOR were consistent with clinical specimens. Inhibition of exosome secretion significantly inhibited inflammatory cell infiltration, and the mammary duct had maintained a better structure in the PCM mouse model. Conclusion. Our results revealed the role of exosomes acting as critical signal introduction facilitators in the progression of plasma cell mastitis and identified potential key genes in the regulation of this process. These results will help to dissect the molecular mechanism of PCM and provide therapeutic targets.