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OBJECTIVE: Multidrug resistance (MDR) to chemotherapeutic drugs is an important reason for clinical chemotherapy failure. So far, the relationship between FOS-like antigen1 (FOSL1) and chemotherapy sensitivity of breast cancer remains unclear. This study investigates the relationship between FOSL1 and chemotherapy sensitivity of breast cancer and its molecular mechanism. METHODS: Doxorubicin-resistant MCF-7/ADR breast cancer cells were transfected with NC (control) or FOSL1 siRNA and assayed for cell viability and relative colony number by MTT assay and colony formation, respectively. The expression level of FOSL1 was detected by immunohistochemistry (IHC). The relationship between FOSL1 and chemotherapy sensitivity was analyzed by a one-way of variance analysis and Pearson's chi-square test among a total of 50 patients with stage II and III breast cancer before and after they received epirubicin-based neoadjuvant chemotherapy (NCT) between 2012 and 2017. RESULTS: The expression of FOSL1 was increased in breast cancer tissues compared with normal breast tissues (P<0.05), and the expression of FOSL1 was decreased after NCT treatment compared with breast cancer tissues (or before NCT). This lower expression of FOSL1 was correlated with chemotherapy resistance or chemotherapy sensitivity (P<0.05). Moreover, the expression level of FOSL1 was markedly lower in NCT-sensitive patients than that of NCT-resistant patients (P<0.05). CONCLUSION: Down-regulation of FOSL1 potentiated chemotherapy sensitivity of breast cancer, and its lower expression attenuated chemotherapeutic drug resistance in human breast cancer cells. FOSL1 might be a drug target for predicting chemotherapy effect in breast cancer.
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BACKGROUND Idiopathic pulmonary fibrosis (IPF) is a deadly disease characterized by excessive collagen in the extracellular matrix (ECM) of the lungs. Collagen is the primary protein component of the ECM. However, the exact mechanisms underlying the formation and deposition of collagen in the ECM under normal and pathological conditions remain unclear. Previous studies showed that lysyl hydroxylase (LH) plays a crucial role in the formation of collagen. Minoxidil is an FDA-approved anti-hypertensive agent that inhibits LH that reduces fibrosis. In this study, we investigated the functional roles of LHs (LH1, LH2, and LH3) in pulmonary fibrosis and the anti-fibrotic effects of minoxidil. MATERIAL AND METHODS Patient serum samples were examined for their expression of procollagen-lysine, 2-oxoglutarate 5-dioxygenases (PLOD) 1-3, the genes encoding LH 1-3. Mice with bleomycin (BLM 2.5 mg/kg)-induced pulmonary fibrosis were administered a minoxidil solution (30 mg/kg) by oral gavage. RESULTS The PLOD mRNA levels were significantly higher in the IPF patients than in the healthy control subjects. Minoxidil suppressed the BLM-induced pulmonary fibrosis in vivo. These effects were associated with blocking TGF-ß1/Smad3 signal transduction and attenuating the expression and activity of LHs, resulting in decreased collagen formation, thus reducing the pulmonary fibrosis. The anti-fibrotic effects of minoxidil may be mediated through competitive inhibition of LHs activity, resulting in decreased pyridine cross-link formation and collagen production and deposition. CONCLUSIONS The results of this study suggest that LH represents a target to prevent or treat pulmonary fibrosis, and minoxidil may provide an effective agent to inhibit LHs.