RESUMEN
BACKGROUND:Sheng-Huangmixture includingChinese medicine Shengmai Decoction and total flavonoids of stems and leaves of radix has been shown to resist inflammation, regulate immune function, and protect ischemic myocardial tissues. However, its effect on the apoptosis of cardiac muscle cels after ischemia/reperfusion injury remains unclear. OBJECTIVE:To investigate the effects ofSheng-Huangmixture on cardiocyte apoptosis and bax and bcl-2 mRNA expression in rats with ischemia-reperfusion injury. METHODS:Thirty-six Sprague-Dawley rats weredivided randomly into six groups: low-dose, moderate-dose and high-doseSheng-Huangmixture, positive control, blank and model groups (n=6). After 7 days of administration, models of myocardial ischemia-reperfusion injury were established. TUNEL was usedto detect myocardial apoptosis. RT-PCR was utilized to measure bax and bcl-2 mRNA expression in the ischemic and reperfusion region. RESULTS AND CONCLUSION:(1) The bcl-2 mRNA expression was significantly higher in the Sheng-Huangmixture group than in the model group (P< 0.05), but bax mRNA expression was significantly lower (P< 0.05). Thus, bcl-2/bax ratio increased. In addition, apoptosis index was more significantly decreased in theSheng-Huangmixture group(P< 0.05). (2) Results demonstrated that Sheng-Huangmixture can protect rat myocardium against ischemia/reperfusion injury, and effectively increase the bcl-2/bax ratio andinhibit the apoptosis of cardiomyocytes, and the underlying mechanism is mediated by up-regulating bcl-2 mRNA expression and down-regulating bax mRNA expression.
RESUMEN
Aberrant glycosylation is a hallmark of most human cancers and affects many cellular properties, including cell proliferation, apoptosis, differentiation, transformation, migration, invasion, and immune responses. Here, we report that N-acetylgalactosaminyltransferase14 (GALNT14), which mediates the initial step of mucin-type O-glycosylation and is heterogeneously expressed in most breast cancers, plays a critical role in the invasion and migration of breast cancers by regulating the activity of MMP-2 and expression of some EMT genes. We have modulated the expression of GALNT14 by RNAi and overexpression in MCF-7 cells. Overexpression of GALNT14 significantly enhanced cell migration and invasion and promoted the proliferation of breast cancer cells. Knockdown of GALNT14 reduced clonogenicity and attenuates cell migration and cell invasion. The mRNAs for N-cadherin, vimentin, E-cadherin, MMP-2, VEGF, and TGF-ß were determined by RT-qPCR involving GALNT14-overexpressing or knockdown MCF-7 cells. Expression profiling revealed the upregulation of N-cadherin, vimentin, MMP-2, VEGF, TGF-ß and the downregulation of E-cadherin in GALNT14 overexpressing cells, with the opposite seen in GALNT14 knockdowns. Gelatin zymography analysis further indicated that overexpression of GALNT14 increased MMP-2 activity in MCF-7 cells. Conversely, downregulation of GALNT14 reduced MMP-2 activity. Promoter analysis revealed that GALNT14 stimulates MMP-2 expression through the AP-1-binding site. Western blot analyses showed that knockdown of GALNT14 significantly reduced the expression of an oncoprotein mucin 1 (MUC1). These findings indicate that GALNT14 contributes to breast cancer invasion by altering the cell proliferation, motility, expression levels of EMT genes, and by stimulating MMP-2 activity, suggesting GALNT14 may be a potential target for breast cancer treatment.