狼毒乙醇提取物限制糖脂代谢阻止小鼠肺癌细胞生长和转移

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采用不同浓度的狼毒乙醇提取物处理体外培养的Lewis肺癌细胞48h,MTT法检测细胞粘附与增殖,transwell小室检测细胞运动,并测定细胞内葡萄糖(Glu)、葡萄糖转运体1(GLUT1)、游离脂肪酸(FFA)和甘油三酯(TG)水平.将小鼠Lewis肺癌细胞分别注射到小鼠腋部皮下和尾静脉建立小鼠Lewis肺癌皮下移植模型和实验性肺转移模型,分成模型组、狼毒乙醇提取物高剂量组和低剂量组,模型建立后次日给药,治疗3周评价狼毒乙醇提取物的抗肿瘤和抗转移作用,检测瘤组织中GLUT1、乳酸脱氢酶(LDH)、琥珀酸脱氢酶(SDH)、FFA和TG水平,并采用免疫组化法比较肺转移肿瘤部位与非肿瘤部位GLUT1和脂肪酸合成酶(FAS)的差异.结果显示,狼毒乙醇提取物对体外培养的Lewis肺癌细胞呈剂量依赖性抑制其粘附、增殖和运动,能降低细胞内Glu,GLUT1,FFA和TG水平.与未治疗的模型小鼠比较,狼毒乙醇提取物呈剂量依赖性减缓肿瘤生长速度、阻止肿瘤转移、延长荷瘤小鼠存活时间.狼毒乙醇提取物能降低瘤组织中GLUT1,LDH,FFA和TG水平,但增加SDH活性.在免疫组化中,与正常肺组织比较,狼毒乙醇提取物也能抑制肺转移肿瘤部位的GLUT1和FAS.以上结果表明,狼毒乙醇提取物能限制肿瘤细胞对葡萄糖和脂肪的利用从而阻止肺癌细胞的生长和转移,是一种有前景的新型潜在抗肿瘤药物. Lewis lung carcinoma cells cultured in vitro were treated with different concentrations of Stellera chamaejasme ethanol extract for 48h. Cell adhesion and proliferation were detected by MTT assay. Transwell chambers were used to detect cell motility. Glucose, glucose transporter 1 (GLUT1) Free fatty acid (FFA) and triglyceride (TG) were determined.Mouse Lewis lung cancer cells were injected into the subcutaneous and tail vein of mice axilla respectively to establish subcutaneous Lewis lung carcinoma model and experimental lung metastasis model, The model rats were administered on the next day after the establishment of the model. The antitumor and anti-metastatic effects of Ethanol extract from S. cerevisiae were evaluated 3 weeks after treatment. The contents of GLUT1, lactate dehydrogenase (LDH) ), Succinate dehydrogenase (SDH), FFA and TG levels were detected by immunohistochemical method.The differences of GLUT1 and fatty acid synthase (FAS) between lung metastases and non-tumor sites were compared by immunohistochemistry.The results showed that ethanol extracts Lewis lung cancer cells cultured in vitro inhibited the adhesion, proliferation and motility in a dose-dependent manner, and decreased the levels of Glu, GLUT1, FFA and TG.Compared with the untreated mice, Ethanol extract showed a dose-dependent Slow down the growth of tumor, prevent tumor metastasis and prolong the survival time of tumor-bearing mice.Ethanol extract of Stellera chamaejasme could decrease the level of GLUT1, LDH, FFA and TG, but increase the activity of SDH.In immunohistochemistry, Tissue comparisons of Ethanol extract of Stellera chamaejasu could also inhibit GLUT1 and FAS in lung metastatic tumor sites.The above results suggest that Ethanol extract of Stellera chamaejasme could limit the utilization of glucose and fat by tumor cells and prevent the growth and metastasis of lung cancer cells, Promising new potential anti-tumor drugs.
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