ABSTRACT
@#To explore the mechanisms by which AKR1C3 induces tumor resistance, human breast cancer cell strain MCF-7/DOX resistant to doxorubicin, MCF-7/ AKR1C3 cells for overexpression of AKR1C3 and MCF-7/DOX-KD cells for knockdown of AKR1C3 in MCF-7/DOX cells were established. Western blot analysis found that AKR1C3 was expressed at a higher level in MCF-7/DOX than MCF-7 wild type cells. Similarly, CCK-8 and DAPI confirmed that MCF-7/ AKR1C3 cells were more resistant to DOX than AKR1C3 wild types as the IC50 was increased 6 times in MCF-7/AKR1C3 cells more than in AKR1C3 wild type cells. Meanwhile, colony formation ability was also enhanced after AKR1C3 was over-expressed in MCF-7 cells.Cytoplasmic/nuclear separation analysis and IF further found that β-catenin nuclear translocation mediated by AKR1C3 was the main reason contributing to the occurrence of DOX-resistant breast cancer cells. β-catenin inhibitor, XAV939, could reverse the AKR1C3 induced doxorubicin resistance in MCF-7 cells.Results indicated that AKR1C3 could be a potential therapeutic target in breast cancer cells.
ABSTRACT
Objective To investigate the effect of sub-anesthesia dose of isoflurane in 60％ oxygen on acute lung injury in aged rats with sepsis.Methods Ninety male Sprague-Dawley rats,aged 12-14 months,weighing 500-800 g,were divided into 3 groups (n=30 each) using a random number table:sham operation group (Sham group),sepsis group (S group),and sepsis plus isoflurane plus oxygen treatment group (S+I+O group).Sepsis was induced by cecal ligation and puncture in S and S+I+O groups.In group S+I+O,0.7％ isoflurane in 60％ oxygen was inhaled for 1 h starting from 1 and 6 h after operation.Eighteen rats were selected in each group and observed for 7 days after operation,and the survival rate was recorded.Six rats were selected in each group at 24 h after operation,and bronchoalveolar lavage fluid (BALF) was collected to determine the protein concentrations (by BCA protein assay),blood samples were collected from the femoral artery for blood gas analysis,PaO2 was recorded,and the oxygenation index was calculated.Six rats in each group were sacrificed at 24 h after operation,the left lung specimens were obtained and stained with hematoxylin and eosin for examination of pathological changes,the right lung specimens were obtained for determination of wet to dry weight ratio (W/D ratio),and blood samples were collected from the right atrium for measurement of the concentrations of interleukin-1β (IL-1β),IL-6,tumor necrosis factor-α (TNF-α),high-mobility group box 1 protein (HMGB1) and IL-10 in serum (by enzyme-linked immunosorbent assay).Results Compared with group Sham,the survival rate was significantly decreased,and the concentrations of IL-1β,IL-6,TNF-α,HMGB1 and IL-10 in serum were increased in S and S+I+O groups,and W/D ratio and protein concentrations in BALF were significantly increased,and the oxygenation index was decreased in group S (P＜0.05).Compared with group S,the survival rate was significantly increased,W/D ratio and protein concentrations in BALF were decreased,the oxygenation index was increased,the concentrations of IL-1β,IL-6,TNF-α and HMGB1 in serum were decreased,and the concentration of serum IL-10 was increased (P＜0.05),and the pathological changes were significantly attenuated in group S+I+O.Conclusion Sub-anesthesia dose of isoflurane in 60％ oxygen can reduce acute lung injury in aged rats with sepsis,and the mechanism may be ralated to inhibiting systemic inflammatory responses.