Protective effects of micro RNA-98-5p targeting Kruppel-like factor 9 against myocardial ischemia-reperfusion injury in rats / 解剖学报

Objective To investigate the protective effect of micro RNA(miR)-98-5p targeting Kruppel-like factor 9(KLF9) against myocardial isehemia-reperfusion(MI/R) injury in rats. Methods Totally 50 rats were randomly divided into sham operation group, model group, miR-98-5p agomir group, agomir-NC group, and miR-98-5p agomir+pcDNA-3. 1-KLF9 group, 10 in each group. MI/R model was established by coronary artery ligation. The pathological changes of myocardial tissue were detected by HE staining. The myocardial apoptosis were detected by TUNEL. The levels of creatine kinase (CK), creatine kinase isoenzymes (CK-MB) and lactate dehydrogenase (LDH) in serum were detected by ELISA. The expression levels of miR-98-5p and KLF9 mRNA were detected by Real-time PCR. The expression of KLF9, Bax and JAK2/STAT3 pathway relative protein were detected by Western blotting. Dual luciferase assay verified the relationship between miR-98-5p and KLF9. Results Compared with the sham operation group, the arrangement of myocardial cells in the model group was disordered, and the myocardial cells appeared necrosis. The apoptosis rate of myocardial cells, serum CK, CK-MB and LDH contents increased, the expression level of miR-98-5p decreased, and the expression levels of KLF9 mRNA and protein, p-JAK2 and p-STAT3 protein increased (P < 0. 05) . After the overexpression of miR-98-5p, the myocardial cells arranged more orderly and the myocardial cell necrosis decreased. The apoptosis rate of myocardial tissue, the contents of CK, CK-MB and LDH in serum and the expression of p-JAK2 and p-STAT3 protein were decreased (P< 0. 05) . The result of dual luciferase assay showed that KLF9 was the target gene of miR-98-5p. The overexpression of KLF9 reversed the effects of miR-98-5p agomir on myocardial injury. Conclusion MiR-98-5p targeting KLF9 can improve the myocardial injury of MI/R rats. The mechanism may be related to the regulation of JAK2/STAT3 signal pathway by miR-98-5p which inhibit myocardial cell apoptosis.

Size-Dependent Biological Effects of Quercetin Nanocrystals.

Quercetin (QE) is an attractive natural compound for cancer prevention due to its beneficial anti-oxidative and anti-proliferative effects. However, QE is poorly soluble in water and slightly soluble in oil, which results in its low oral bioavailability and limits its application in the clinic. The aim of this study was to prepare QE nanocrystals (QE-NCs) with improved solubility and high drug loading, furthermore, the size-dependent anti-cancer effects of QE-NCs were studied. We prepared QE-NCs with three different particle sizes by wet milling, then, cell proliferation, migration and invasion were studied in A549 cells. The QE-NCs had antitumor effects in a dose- and size-dependent manner. Compared with the large particles, the small particles had a strong inhibitory impact on cell biological effects (p < 0.05 or p < 0.01). Moreover, Western blot assay indicated that QE-NCs may inhibit the migration and invasion of A549 cells by inhibiting the STAT3 signaling pathway, and the particle size may have an effect on this process. In this study, it was proven that NCs could dramatically enhance the anticancer efficacy of QE at the cellular level. In addition, particle size had a considerable influence on the dissolution behavior and antitumor effects of NCs.

Effects of quercetin on suppressing migration and invasion of A549 cells via the STAT3 signaling pathway / 国际药学研究杂志

Objective To investigate the effect of quercetin on suppressing the proliferation,migration and invasion of A549 cells via the signal transducer and activator of transcription 3(STAT3)signaling pathway. Methods The A549 cells were cultured in vitro and treated with quercetin at various concentrations(0,7.5,15,30,60 and 120μmol/L)for 24 h,48 h and 72 h. The proliferation of A549 and the 50%inhibitory concentration(IC50)were measured by the cell counting kit-8(CCK-8). The A549 cells treated for 24 h were randomly divided into 4 groups:the blank control,15 and 30 μmol/L quercetin,and 3 μg/ml cisplatin(the positive control) groups. The effect of quercetin on adhesion rate was detected by the cell adhesion assay;the cell migration ability was evaluated by the wound healing assay;the cell invasion ability was evaluated by the Transwell chamber assay;the expression of STAT3 and phosphory?lated-STAT3(p-STAT3)proteins were detected by Western blot assay. Results Quercetin inhibited A549 cell growth dose-depend?ently. Compared with the blank control group,quercetin could significantly inhibit the adhesion rate,migration ability and invasion of A549 cells(P<0.05 or P<0.01);compared with the blank control group,quercetin significantly inhibited STAT3 and p-STAT3 ex?pression level(P<0.05 or P<0.01). Conclusion Quercetin could inhibit the proliferation,migration and invasion of A549 cells, and the mechanism is libely related to the STAT3 signal pathway.

Effects of quercetin on suppressing migration and invasion of A549 cells via the STAT3 signaling pathway / 国际药学研究杂志

Objective To investigate the effect of quercetin on suppressing the proliferation, migration and invasion of A549 cells via the signal transducer and activator of transcription 3 (STAT3) signaling pathway. Methods The A549 cells were cultured in vitro and treated with quercetin at various concentrations (0,7.5,15,30,60 and 120 µmol/L) for 24 h,48 h and 72 h. The proliferation of A549 and the 50% inhibitory concentration (IC50) were measured by the cell counting kit-8 (CCK-8). The A549 cells treated for 24 h were randomly divided into 4 groups: the blank control, 15 and 30 µmol/L quercetin, and 3 µg/ml cisplatin(the positive control) groups. The effect of quercetin on adhesion rate was detected by the cell adhesion assay; the cell migration ability was evaluated by the wound healing assay; the cell invasion ability was evaluated by the Transwell chamber assay; the expression of STAT3 and phosphorylated-STAT3 (p-STAT3) proteins were detected by Western blot assay. Results Quercetin inhibited A549 cell growth dose-dependently. Compared with the blank control group, quercetin could significantly inhibit the adhesion rate, migration ability and invasion of A549 cells (P<0.05 or P<0.01); compared with the blank control group, quercetin significantly inhibited STAT3 and p-STAT3 expression level (P<0.05 or P<0.01). Conclusion Quercetin could inhibit the proliferation, migration and invasion of A549 cells, and the mechanism is libely related to the STAT3 signal pathway.

The significance of microRNA-184 on JAK2/STAT3 signaling pathway in the formation mechanism of glioblastoma.

Glioblastoma is a type of glioma with a relatively higher degree of malignancy that may result in severe intracranial hypertension and focal symptoms. Surgery is the preferred treatment modality. Combination therapy including radiotherapy, chemotherapy, gene therapy, immunotherapy and targeted therapy have also been employed. However, due to the invasiveness and pathogenesis of the disease, such treatments do not yield satisfactory outcomes. The aim of the present study was to examine the expression of microRNA (miR)-184 in Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway in the mechanism of glioblastoma formation, thus providing a new basis for the mechanism of glioblastoma induction. The LN18 cell line was employed in the present study. After undergoing thawing, culturing and passaging processes, the cells were divided into the set control group, miR-184 mimic group (transfer miR-184 simulator) and miR-184 group. The expression of miR-184 was detected using quantitative polymerase chain reaction. An MTT assay was used to detect the proliferation ability of glioma cells, and clone formation ability was also detected. The cell scratch and invasion assays were used to identify the cell invasion ability. Western blotting was performed to detect the expression level of p-JAK2 and p-STAT3 proteins. The results showed that compared to the control group, the expression of miR-184 in the miR-184 mimic group increased. Cell proliferation, as well as clone formation and invasion ability were enhanced. The number of cells penetrating septum, as well as the expression of p-JAK2 and p-STAT3 proteins were increased. Differences were statistically significant (P<0.05). By contrast, compared to the control group, the expression of miR-184 in the miR-184 inhibitory group decreased. Cell proliferation, as well as clone formation and invasion ability were reduced. The number of cells penetrating septum, as well as the expression of p-JAK2 and p-STAT3 proteins were reduced. Differences were statistically significant (P<0.05). In conclusion, the results of the present study have shown that miR-184 may be involved in the formation of glioblastoma and influence the expression of JAK2/STAT3 signaling pathway.