RESUMEN
Gastric cancer (GC) remains poor prognosis and survival issues due to the resistance of chemotherapies, such as cisplatin. The long non-coding RNA small nucleolar RNA host gene 7 (lncRNA-SNHG7) is known as an oncogenic molecule in diverse cancers. Here, we demonstrate that SNHG7 was significantly upregulated in gastric cancer and positively correlated with cisplatin resistance of gastric cancer cells that SNHG7 was significantly upregulated in cisplatin resistant cells. Silencing SNHG7 dramatically sensitized cisplatin resistant cells. In contrast, a negative correlation between lncRNA-SNHG7 and miR-34a was found that miR-34a was downregulated in gastric cancer patient tissues and significantly sensitized cisplatin resistant gastric cancer cells. Intriguingly, bioinformatical analysis indicated miR-34a has putative biding site for SNHG7 and such negative association between SNHG7 and miR-34a was verified in gastric cancer tissues. The cisplatin resistant cells displayed increased glycolysis rate and SNHG7 promoted cellular glycolysis rate of gastric cancer cells. Luciferase assay illustrated LDHA, a glycolysis enzyme, was the direct target of miR-34a. Importantly, inhibiting SNHG7 successfully suppressed LDHA expressions and sensitized cisplatin resistant cells and such inhibitory effects could be recovered by further anti-miR-34a. These findings suggest an important regulator mechanism for the SNHG7-mediated cisplatin resistance via miR-34a/LDHA-glycolysis axis.
Asunto(s)
Cisplatino/farmacología , MicroARNs/metabolismo , ARN Largo no Codificante/metabolismo , Neoplasias Gástricas/tratamiento farmacológico , Antineoplásicos/farmacología , Resistencia a Antineoplásicos , HumanosRESUMEN
Rapid and effective hemostasis for a noncompressible hemorrhage is the key to control bleeding and reduce mortality. Chitosan (CS) has been widely used as a popular hemostatic dressing; however, irregularly shaped wounds present in emergencies limit the performance of CS powder. To improve the hemostatic effect of CS, we modified it with poly(vinyl alcohol) (PVA), a fast-swelling sponge triggered by water. The novel synthetic PVA-CS was prepared by cross-linking PVA and CS during foaming and crosslinking reactions. Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM) and X-ray diffraction were utilized to analyze the characteristics of PVA-CS. In vitro, the swelling ratio and blood clotting ability were evaluated in different groups with various weight ratios or degrees of deacetylation of the CS, and the cytocompatibility and cell attachment on the material were analyzed by human dermal fibroblast (HDF) cell testing. In vivo, the hemostatic effects were evaluated in Sprague-Dawley rats and Bama miniature pigs in a femoral artery hemorrhage model or gunshot wound experiment. PVA-CS presents robust mechanical strength, rapid water-triggered swelling and a fast absorption speed. As compared with gauze and PVA, which are widely used in first aid, PVA-CS sponges showed an improved blood clotting ability and increased blood cell and platelet adhesion and activation. The PVA-CS sponges also showed high biocompatibility in cell viability, cell proliferation and cell attachment bioassays. Furthermore, in vivo evaluation of the PVA-CS sponges revealed excellent hemostatic performance and enhanced wound healing with increased re-epithelialization and decreased granulation tissues. The results of this study strongly support the use of these composite sponges for noncompressible hemorrhage in acute trauma and ballistic injuries.
Asunto(s)
Vendajes , Materiales Biocompatibles Revestidos , Hidrogeles , Cicatrización de Heridas , Heridas por Arma de Fuego/terapia , Animales , Coagulación Sanguínea/efectos de los fármacos , Células Cultivadas , Quitosano/química , Materiales Biocompatibles Revestidos/química , Materiales Biocompatibles Revestidos/farmacología , Arteria Femoral/lesiones , Fibroblastos , Hemostáticos/química , Hemostáticos/farmacología , Humanos , Hidrogeles/química , Hidrogeles/farmacología , Ratones , Ratones Endogámicos BALB C , Alcohol Polivinílico/química , Ratas , Ratas Sprague-Dawley , PorcinosRESUMEN
OBJECTIVE: To investigate the effect of elemene on reversing chemoresistance to adriamycin (ADM) in human stomach cancer cell, and explore its possible mechanism. METHODS: SGC7901/ADM were divided imto two groups: control group and elemene treatment group. The cytotoxicity of ADM on SGC7901/ADM was determined by MTT assay. The activity of nuclear factor-kappa B (NF-kappaB) was measured by immunohistochemical staining. The apoptosis rate of stomach cancer cell line was determined by flow cyotometric analysis. RESULTS: The immunohistochemical staining result showed that the activity of NF-kappaB in SGC7901/ADM was increased after treated with ADM for 9 - 12 h, while that of the elemene treatment group decreased with the increasing of the elemene concentration and the lowest level was 8 - 12%. The apoptosis rate of SGC7901/ADM stomach cancer cell line was increased with the increasing of elemene concentration. At the same elemene concentration, the apoptosis rate increased with ADM treatment time prolonged. MTT result showed that the non-cytotoxic dose of elemene had synergistic effect on rilling SGC7901/ADM stomach cancer cell line and was in a dose-dependant manner. CONCLUSION: The inhibitory effect of elemene on reversing chemoresistance to ADM in human stomach cancer cell line maybe related to inhibiting NF-kappaB activity.