IFN-γ inhibits ovarian cancer progression via SOCS1/JAK/STAT signaling pathway.

PURPOSE: Ovarian cancer (OC) is a common malignancy, and IFN-γ, a multifunctional cytokine, is unveiled to impede the multiplication and enhance apoptosis in diverse tumor cells in previous research. Nonetheless, its function and mechanism in OC are blurred. METHODS: OC cell lines SKOV3 and OVCAR3 were dealt with different concentrations (0-40 ng/ml) of IFN-γ. CCK-8 experiment was utilized to examine cell multiplication; Flow cytometry was executed to detect apoptosis and cell cycle; Wound healing assay was utilized to detect cell migration; and Transwell experiment was implemented to examine cell invasion. qRT-PCR analysis was applied to detect STAT5, STAT3, JAK2 and JAK3 mRNA expression in OC cell lines. Western blot experiment was applied to detect the protein and phosphorylation levels of SOCS1, STAT5 and STAT3. RESULTS: IFN-γ suppressed OC cell multiplication in a concentration-dependent manner. Relative to the control group, IFN-γ restrained OC cell migration, invasion, enhanced apoptosis and prevented cell transformation from G0/G1 to S phase. Further analysis revealed that IFN-γ up-modulated SOCS1 expression and impeded STAT5 and STAT3 protein phosphorylation levels, and knockdown of SOCS1 partially counteracted the inhibitory effect of IFN-γ on STAT5 and STAT3 protein phosphorylation levels. CONCLUSION: IFN-γ represses OC progression by facilitating SOCS1 to suppress STAT3 and STAT5 protein phosphorylation.

Atomized paclitaxel liposome inhalation treatment of bleomycin-induced pulmonary fibrosis in rats.

We sought to determine the efficacy of atomized paclitaxel liposome inhalation treatment of pulmonary fibrosis in a bleomycin-induced rat model. Forty male Sprague-Dawley rats were randomly divided into four groups: healthy control, pulmonary fibrosis without treatment, paclitaxel liposome inhalation-treated, and intravenous paclitaxel liposome-treated. Fibrosis was induced by bleomycin injection. A total of 20 mg/kg paclitaxel liposome was administered by inhalation every other day for a total of 10 doses. The intravenous group received 5 mg/kg paclitaxel liposome on days 1, 7, 14, and 21. We observed the general condition, weight change, survival index, and pathological changes in the lung tissue of the rats. Quantitative analysis of collagen types I and III and transforming growth factor (TGF)-ß1 expression in the lungs was also performed. The paclitaxel liposome inhalation and intravenous delivery methods improved survival index and pulmonary fibrosis Ashcroft score, and decreased the thickness of the alveolar interval. No obvious difference was found between the two groups. Compared with the untreated group, paclitaxel liposome inhalation and intravenous injection significantly reduced the levels of collagen types I and III and TGF-ß1 expression equally. In conclusion, atomized paclitaxel liposome inhalation protects against severe pulmonary fibrosis in a bleomycin-induced rat model. This delivery method has less systemic side effects and increased safety over intravenous injection.

Effect of melatonin on oncosis of myocardial cells in the myocardial ischemia/reperfusion injury rat and the role of the mitochondrial permeability transition pore.

We aimed to evaluate the effect of melatonin on myo-cardial cell oncosis in the myocardial ischemia/reperfusion injury rat, and the role of the mitochondrial permeability transition pore (MPTP) therein. Sprague Dawley rats (N = 60) were randomly divided into five groups of 12 rats each: control, ischemia/reperfusion (I/R), melatonin treatment (MT), melatonin treatment + atractyloside (MT+ATR), and atractyloside (ATR). We prepared the myocardial ischemia/reperfusion model by reperfusion after the left anterior descending coronary artery was ligated for 30 min. The MT rats were given a 10 mg/kg MT intra-venous injection immediately thereafter; the MT+ATR rats were also given a 5 mg/kg ATR intravenous injection 15 min before the ischemia; the ATR rats were given the ATR injection only. After 2-h re-perfusion, myocardial tissue was extracted, the infarction size was determined, and myocardial ultrastructures were observed using electron microscopy. The expression level of the preoncosis receptor (porimin), which can induce membrane injury, was determined by western blot; the nicotinamide adenine dinucleotide (NAD(+)) content was determined spectrophotometrically. The four treatment groups showed upregulat-ed expression of myocardial porimin, increased myocardial infarction size, and reduced NAD(+) content (P < 0.05). Compared with the I/R and MT+ATR groups, MT rats showed downregulated expression of myo-cardial porimin, reduced myocardial infarct size, and increased myo-cardial cell NAD(+) content (P < 0.05). The above indices between the ATR and MT+ATR groups were not significantly different (P > 0.05). Thus, MT might protect myocardial ischemia/reperfusion rats by inhibiting MPTP opening and reducing myocardial cell oncosis.