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Matrine induces apoptosis via targeting CCR7 and enhances the effectof anticancer drugs in non-small cell lung cancer invitro

机译:苦参碱通过靶向CCR7诱导凋亡并增强其作用非小细胞肺癌中抗癌药物的研究体外

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摘要

This study mainly investigated the effects of matrine on cell apoptosis and theeffects of anticancer drugs in non-small cell lung cancer (NSCLC) cell lines(A549 and LK2 cells). The results showed that matrine (≥10 μM) caused asignificant inhibition on cell viability and 10 and 100 μM matrine induced cellapoptosis via influencing p53, bax, casp3, and bcl-2 expressions in A549 cells.In addition, matrine significantly down-regulated C-C chemokine receptor type 7(CCR7) expression, and blocking the down-regulation of CCR7 by exogenouschemokine ligand 21 (CCL21) treatment alleviated matrine-caused effects ofapoptosis genes in A549 cells. The results were further validated in LK2 cellsthat matrine regulated apoptosis gene expressions, which were reversed by CCL21treatment. Furthermore, matrine enhances the effects of cisplatin,5-fluorouracil, and paclitaxel in A549 cells, and the anticancer effects exhibita dosage-dependent manner. In summary, matrine induced cell apoptosis andenhanced the effects of anticancer drugs in NSCLC cells; the mechanism might beassociated with the CCR7 signal.
机译:本研究主要研究苦参碱对细胞凋亡和凋亡的影响。癌药物在非小细胞肺癌(NSCLC)细胞系中的作用(A549和LK2细胞)。结果显示苦参碱(≥10μM)引起显着抑制细胞活力以及10和100μM苦参碱诱导的细胞通过影响A549细胞中的p53,bax,casp3和bcl-2表达来诱导细胞凋亡。此外,苦参碱显着下调了7型C-C趋化因子受体(CCR7)表达,并阻止外源CCR7的下调趋化因子配体21(CCL21)的治疗减轻了苦参碱引起的A549细胞中的凋亡基因。结果在LK2细胞中得到进一步验证苦参碱调节细胞凋亡基因表达,被CCL21逆转治疗。此外,苦参碱还增强了顺铂的作用,5-氟尿嘧啶和紫杉醇在A549细胞中的抗癌作用剂量依赖性的方式。总之,苦参碱诱导细胞凋亡和增强NSCLC细胞中抗癌药的作用;该机制可能是与CCR7信号相关。

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