小陷胸汤通过G2/M期阻滞抑制A549和H1299细胞增殖并抑制其侵袭和转移(英文)

Xiaoxianxiong Decoction inhibits cell growth through G_2/M phase cell cycle arrest and migration and invasion ability of A549 and H1299 cells

目的:从体内体外实验共同着手,探讨祛痰剂小陷胸汤对非小细胞肺癌的抑制作用。方法:采用细胞增殖抑制、侵袭和转移以及细胞周期分析等进行体外研究。裸鼠异体移植A549肿瘤模型用于体内实验研究。MTT和软琼脂克隆形成实验用于细胞增殖测定;划痕和Transwell检测肺癌细胞的侵袭和转移能力;流式和PCR用于细胞周期分析。结果:通过细胞活力的丧失,形态变化以及G2/M周期阻滞的分析,发现A549和H1299细胞在小陷胸汤的干预下发生生长阻滞。PCR结果显示细胞周期相关基因GADD45A上调,CCNB1和CCNB2下调。此外,在小陷胸汤的作用下,A549和H1299细胞侵袭和转移能力呈剂量依赖性下降。通过小鼠右侧腋部皮下接种A549细胞建立肺癌小鼠异体移植模型,小陷胸汤处理后能够抑制肿瘤的生长。结论:小陷胸汤干预后肺癌细胞生长阻滞以及细胞的周期阻滞阐明小陷胸汤可以作为一种新的治疗肺癌的药物。小陷胸汤在体内外实验中减少肿瘤发生及转移潜能,这对临床治疗肿瘤至关重要。

Objective： To further investigate the effects of expectorant Xiaoxianxiong Decoction （XXXD） on the growth of non-small cell lung cancer （NSCLC） cells by a series of in vivo and vitro experiments. Methods： Cell proliferation, invasion, migration and cell cycle arrest assay were applied for in vitro evaluation; Xenograft A549 tumor model was used for in vivo evaluation. MTT and Soft agar colony formation assay were used for cell proliferation; Scratch assay and Transwell were applied in motility and invasion assay; Flow cytometre and quantitative RT-PCR were applied for cell-cycle. Results： Exposure of A549 and H1299 cells to X.XXD resulted in growth arrest, evidenced by loss of cell viability and morphological changes and G：/M phase cell cycle arrest. PCR showed up-regulated of GADD45A and down-regulated of CCNB1 and CCNB2. Furthermore, migration and invasion ability were decreased by XXXD in a dose-dependent manner. Mouse xenograft models of lung cancer were established by subcutaneously implanted into the right flank region with A549 cells, XXXD had an inhibitory effect on tumor growth. Conclusion： Growth arrest and cell cycle arrest by XXXD treatment provide an innovative argument for the use of XXXD as a treatment compound. In vivo and vitro experiments utilizing XXXD to reduce tumorigenesis and metastatic potential will be crucial to further justify clinical application.