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Anti-tumor effect of chitin oligosaccharide plus cisplatin in vitro and in vivo

机译:几丁质寡糖加顺铂在体内外的抗肿瘤作用

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Background: Lung cancer is one of the most common malignant tumors in human beings, and cisplatin is a widely used chemotherapy drug, but its clinical application is limited because of its dose-dependent toxicity and drug resistance. Chitin is known to have various biological activities including anti-tumor, but the insoluble feature in common solvents greatly restricts its application. Chitin oligosaccharide is a small water-soluble molecule degraded from chitin without any toxic effect. Methods: Chitin oligosaccharide was adopted to investigate the effects on lung adenocarcinoma A549 cells and tumor xenografts of nude mice. The experiments were divided into control group, chitin oligosaccharide group, cisplatin group and combination group. MTS assay, cell scratch test and migration assay were used to observe the proliferation and migration of A549 cells, and Western blot was used to detect the expression levels of caspase8, caspase3 and BAK. Ki67 and P53 expressions of tumor xenografts were detected to explore the effects of drugs on tumor prognosis. Results: The results in vitro showed that chitin oligosaccharides could inhibit the proliferation and migration of A549 cells, and the effect was superior to chitin oligosaccharide or cisplatin when combined with cisplatin. Chitin oligosaccharide plus cisplatin up-regulated the expression level of caspase8 and caspase3, while had minor influence on the expression level of BAK. In vivo experiments showed that chitin oligosaccharide plus cisplatin could down-regulate the expression level of Ki67, while had minor influence on the expression level of P53. Conclusion: The study demonstrated that chitin oligosaccharide plus cisplatin had positive synergistic effects, and it is possible to improve the prognosis of lung adenocarcinoma patients by up-regulating the expression level of caspase8, caspase3 and down-regulating the expression level of Ki67.
机译:背景:肺癌是人类最常见的恶性肿瘤之一,顺铂是一种广泛使用的化疗药物,但由于其剂量依赖性毒性和耐药性,其临床应用受到限制。已知几丁质具有多种生物活性,包括抗肿瘤作用,但是普通溶剂中的不溶性特征极大地限制了它的应用。几丁质寡糖是一种从几丁质降解的水溶性小分子,无任何毒性作用。方法:采用几丁质低聚糖对裸鼠肺腺癌A549细胞和肿瘤异种移植的影响。实验分为对照组,几丁质寡糖组,顺铂组和联合组。 MTS法,细胞划痕试验和迁移法观察A549细胞的增殖和迁移,Western blot检测caspase8,caspase3和BAK的表达水平。检测肿瘤异种移植物的Ki67和P53表达,以探讨药物对肿瘤预后的影响。结果:体外实验结果表明,几丁质寡糖可抑制A549细胞的增殖和迁移,与几丁质寡糖或顺铂联合使用效果更佳。几丁质寡糖加顺铂上调了caspase8和caspase3的表达水平,而对BAK的表达影响较小。体内实验表明,几丁质寡糖加顺铂可以下调Ki67的表达水平,而对P53的表达水平影响较小。结论:该研究表明几丁质寡糖与顺铂具有协同增效作用,可通过上调caspase8,caspase3的表达水平和下调Ki67的表达水平来改善肺腺癌患者的预后。

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