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目的探讨异鼠李素体内外对肺癌增殖的影响及初步研究其抗肿瘤机制。方法将不同浓度异鼠李素加入体外培养的人A549细胞,用MTT法,3H-TdR掺入法等测定体外抗瘤活性,用流式细胞仪、彗星电泳、免疫组化等观察其对肿瘤细胞凋亡的诱导作用;采用Lewis细胞C57BL/6鼠移植瘤,观察药物对移植瘤的影响。结果异鼠李素处理A549细胞后,细胞形态出现典型凋亡特征,下调bcl-2基因,PCNA蛋白表达;上调抑癌基因P53、bax及caspase-3基因。实验观察到,异鼠李素在体内也具有明显的抗肿瘤作用,可显著降低癌细胞增殖指数,诱导Lewis肺癌凋亡,其机理可能与下调PCNA和bcl-2的表达,上调caspase-3、bax表达有关。结论异鼠李素抑制肿瘤细胞的生长增殖,诱导细胞凋亡是其抗肿瘤作用主要机制之一,是一种有较好前景的抗肿瘤的新型中药单体。
Objective To investigate the effect of isorhamnetin on the proliferation of lung cancer in vitro and in vivo and to study its antitumor mechanism. Methods Different concentrations of isorhamnetin were added into human A549 cells in vitro. The antitumor activity was determined by MTT assay and 3H-TdR incorporation assay. The effects of isorhamnetin on tumor cells were analyzed by flow cytometry, comet assay and immunohistochemistry. C57BL / 6 mice were transplanted with Lewis cells to observe the effects of the drugs on the xenografts. Results Isorhamnetin treatment A549 cells, the typical morphological characteristics of apoptosis cells, down regulation of bcl-2 gene, PCNA protein expression; up-regulation of tumor suppressor genes P53, bax and caspase-3 gene. It was observed experimentally that isorhamnetin also has a significant anti-tumor effect in vivo, which can significantly reduce the proliferation index of cancer cells and induce the apoptosis of Lewis lung cancer. The mechanism may be related to the down-regulation of the expression of PCNA and bcl-2, up-regulation of caspase-3, bax expression. Conclusion Isorhamnetin inhibits the growth and proliferation of tumor cells and induces apoptosis is one of the main mechanisms of its anti-tumor effect. It is a promising new anti-tumor traditional Chinese medicine monomer.