Abstract:
At present, there are still many problems in the treatment of lung cancer, such as high cost, side effects and low quality of life. The advantages of traditional Chinese medicine (TCM) in the treatment of lung cancer are reflected. Berberine has been increasingly popular in colorectal cancer treatment, but little is known about its bioactivity against non-small cell lung cancer (NSCLC). Cell proliferation, cell apoptosis, cDNA microarray, gene and protein expression, and NSCLC transplanted tumour growth were performed. Berberine suppressed NSCLC cell proliferation and colony formation in vitro and inhibited NSCLC tumour growth in subcutaneously transplanted tumour lung tumour models, leading to prolonged survival of tumour-bearing mice. However, berberine did not induce the cleavage of Caspase 3 and PARP1, and could not induce apoptosis in all NSCLC cells. Moreover, 646 genes were differentially expressed upon berberine administration, which were involved in seven signal pathways, such as DNA replication. In cDNA microarray, berberine downregulated the expression of RRM1, RRM2, LIG1, POLE2 that involving DNA repair and replication. Our findings demonstrate that berberine inhibits NSCLC cells growth through repressing DNA repair and replication rather than through apoptosis. Berberine could be used as a promising therapeutic candidate for NSCLC patients.
摘要:
目前,肺癌的治疗还有很多问题,例如高成本,副作用和生活质量低。体现了中医药在肺癌治疗中的优势。小檗碱在结直肠癌治疗中越来越受欢迎,但对其抗非小细胞肺癌(NSCLC)的生物活性知之甚少。细胞增殖,细胞凋亡,cDNA微阵列,基因和蛋白质表达,进行NSCLC移植肿瘤生长。小檗碱在体外抑制NSCLC细胞增殖和集落形成,并在皮下移植的肿瘤肺肿瘤模型中抑制NSCLC肿瘤生长,导致荷瘤小鼠的存活时间延长。然而,小檗碱不诱导Caspase3和PARP1的裂解,也不能诱导所有NSCLC细胞凋亡。此外,646个基因在小檗碱给药后差异表达,涉及七种信号通路,比如DNA复制。在cDNA微阵列中,小檗碱下调RRM1,RRM2,LIG1,POLE2的表达,涉及DNA修复和复制。我们的发现表明,小檗碱通过抑制DNA修复和复制而不是通过凋亡来抑制NSCLC细胞的生长。小檗碱可作为NSCLC患者的有希望的候选药物。