Salbutamol [KLH]

Vascular endothelial cell apoptosis is regulated by microRNA-133a (miR-133a), which participates in the formation of atherosclerotic (AS) plaques, leading to the development of several cardiovascular diseases. Salidroside (SAL), the main component of Rhodiola, is considered to exert anti-AS effect; however, its mode of action remains unclear. Thus, the present study aimed to determine whether SAL inhibits endothelial cell apoptosis through the miR-133a pathway. Cultured human coronary artery endothelial cells (HCAECs) were exposed to oxidized low-density lipoprotein (ox-LDL). Cell viability and cytotoxicity were monitored by MTT assay. In parallel, the mRNA expression levels of miR-133a and Bcl-xL, and the protein levels of anti-apoptotic Bcl-xL and activated caspase-3 were measured. The apoptotic levels were examined by flow cytometry. Furthermore, the effects of silencing and overexpressing miR-133a on the parameters mentioned above were evaluated. Exposure to ox-LDL induced an increase in the expression of miR-133a, with a concomitant decrease in the level of Bcl-xL in the HCAECs; these effects were reversed by treatment with SAL. Importantly, the effects of SAL were impaired upon the silencing of miR-133a, whereas the overexpression of miR-133a partly restored the effects of SAL. On the whole, the findings of the present study demonstrate that SAL inhibits the ox-LDL-induced upregulation of miR-133a expression, while promoting the expression of Bcl-xL, thereby preventing endothelial cell apoptosis.

Cancer cell metastasis is a leading cause of mortality in cancer patients. Therefore, revealing the molecular mechanism of cancer cell invasion is of great significance for the treatment of cancer. In human patients, the hyperactivity of transcription factor Spalt-like 4 (SALL4) is sufficient to induce malignant tumorigenesis and metastasis. Here, we found that when ectopically expressing the Drosophila homologue spalt (sal) or human SALL4 in Drosophila, epithelial cells delaminated basally with penetration of the basal lamina and degradation of the extracellular matrix, which are essential properties of cell invasion. Further assay found that sal/SALL4 promoted cell invasion via dMyc-JNK signaling. Inhibition of the c-Jun N-terminal kinase (JNK) signaling pathway through suppressing matrix metalloprotease 1, or basket can achieve suppression of cell invasion. Moreover, expression of dMyc, a suppressor of JNK signaling, dramatically blocked cell invasion induced by sal/SALL4 in the wing disc. These findings reveal a conserved role of sal/SALL4 in invasive cell movement and link the crucial mediator of tumor invasion, the JNK pathway, to SALL4-mediated cancer progression.