ABSTRACT
We investigated the inhibitory effect and mechanism of action of bruceantin (BCT) on the proliferation, invasion and migration of non-small cell lung cancer (NSCLC) cells. The cytotoxic activity of BCT was measured by MTT assay; a colony forming assay, wound healing assay, and a Transwell assay were used to investigate the anti-proliferative, anti-migration, and anti-invasion effects, respectively; immunoblotting and RT-qPCR were used to detect the expression of related proteins, miRNA, and mRNA, respectively, that were involved in cell proliferation, migration, and invasion. Two gene prediction websites were used to predict the downstream target gene of miRNA. Our results show that BCT has a potent cytotoxic effect on NSCLC cell lines, with a half maximal inhibitory concentration (IC50) of BCT against H1299, PC-9, and A549 of 0.12 ± 0.02, 0.31 ± 0.20, and 2.07 ± 0.70 μmol·L-1, respectively. When H1299 cells were treated with 0.03, 0.15, and 0.75 μmol·L-1 BCT for 24 h, the proliferation, migration, and invasive ability were inhibited in a concentration-dependent manner. It is worth noting that the expression level of miRNAs related to cell migration and invasion, such as miR-29a-3p, miR-21-3p, miR-183-5p, and miR-34b-5p increased with the concentration of BCT, especially for miR-29a-3p. Using the two gene prediction websites, we predict that integrin β1 (ITGB1) may be the target gene of miR-29a-3p; immunoblot results further show that a variety of proteins related to cell proliferation, migration, and invasion, such as various proteins of the integrin family, β-catenin, p-Src, and vascular endothelial growth factor, all decreased in a concentration-dependent manner, among which the reduction of ITGB1 protein was the most obvious. RT-qPCR results showed that there was no change in ITGB1 mRNA expression. We speculate that BCT might inhibit the expression of ITGB1 protein by up-regulating miR-29a-3p independent of its mRNA level. The in-depth mechanism needs to be further explored. This study suggests that BCT has the potential for further development in the treatment of NSCLC.
ABSTRACT
<p><b>OBJECTIVE</b>To explore an optimal oxygen saturation for extremely preterm infants based on a systemic review of the published studies.</p><p><b>METHODS</b>A Meta analysis of the published studies by the NeOProM Group which compared the outcomes of extremely preterm infants (gestational age <28 weeks) maintained in either a low (85%-89%) or high (91%-95%) oxygen saturation (SpO2) by using the STATA 12.0. The outcomes measured included the mortality and the incidences of retinopathy of prematurity (ROP), necrotizing enterocolitis of newborn (NEC), broncho-pulmonary dysplasia (BPD), intraventricular hemorrhage (IVH) and patent ductus arteriosus (PDA).</p><p><b>RESULTS</b>Three studies were included, in which 2 460 infants were assigned into the low SpO2 group and 2 459 infants in the high SpO2 group. The Meta analysis demonstrated that the risk of mortality before discharge or at the age of 18 months increased in the low SpO2 group compared with the high SpO2 group (RR: 1.19; 95%CI: 1.05-1.35); the risk of ROP decreased in the low SpO2 group (RR: 0.73; 95%CI: 0.53-1.00); the risk of NEC increased in the low SpO2 group (RR: 1.26; 95%CI: 1.06-1.49). There was no significance in the incidences of BPD, IVH and PDA between the two groups.</p><p><b>CONCLUSIONS</b>Maintaining SpO2 at 85%-89% may decrease the incidence of ROP, but increase the mortality rate and the incidence of NEC in extremely premature infants.</p>