摘要
目的探究天竺葵素(PEL)抑制肺癌进展的作用和机制。方法利用SwissTarget和TargetNet软件预测PEL的靶点,下载TCGA;USC数据矩阵和临床信息,进行差异基因分析。分别以不同浓度PEL处理细胞,观察细胞活性变化;分别用PEL、干扰KIF11(shKIF11)慢病毒载体、pcDNA-KIF11质粒处理肺癌细胞NCI-H1975、NCI-H292,观察PEL对细胞增殖、迁移及侵袭的影响。腋下注射NCI-H1975细胞建立裸鼠荷瘤模型,隔天腹腔注射3 mg/kg PEL,观察PEL对裸鼠肿瘤生长的影响。结果 KIF11为PEL潜在靶点、肺癌中表达上调以及在临床分期Ⅱ~Ⅳ、T2~T4分期组中高表达的共同基因,且与肺癌患者的淋巴结转移(N分期)相关。肺癌裸鼠荷瘤模型中,与对照组比较,PEL组裸鼠肿瘤组织体积、质量及Ki67阳性表达明显降低(P<0.05)。NCI-H1975、NCI-H292细胞中,与对照组比较,PEL组细胞活性、迁移能力及侵袭数明显降低(P<0.05);与杂序的短发卡RNA阴性对照(shNC)组比较,shKIF11 1#组和shKIF11 2#组KIF11表达、细胞活性、迁移能力及侵袭数明显降低(P<0.05);与PEL组比较,PEL+KIF11组KIF11表达、细胞活性、迁移能力及侵袭数明显升高(P<0.05)。结论 PEL可抑制肺癌细胞增殖、迁移及侵袭,其作用机制可能与靶向抑制KIF11表达有关。
Objective To explore the effect and mechanism of pelargonidin(PEL) on inhibiting the progression of lung cancer. Methods The target of PEL was predicted by SwissTarget and TargetNet software. TCGA;USC data matrix and clinical information were downloaded to analyze differential genes. The cells were treated with different concentrations of PEL to observe changes of cells activity. The lung cancer cell lines NCI-H1975 and NCI-H292 were treated with PEL, shKIF11 lentiviral vector and pcDNA-KIF11 plasmid, respectively. The effects of PEL on proliferation, migration and invasion of cells were observed. NCI-H1975 cells were injected via armpit to generate tumor-bearing models of nude mice. Then, they were given intraperitoneal injection of 3 mg/kg PEL every other day to observe the effects of PEL on tumor growth in nude mice. Results KIF11 was the potential target of PEL, and was also the common gene that was up-regulated in lung cancer and was highly expressed in stage Ⅱ~Ⅳ and T2~T4 stage groups. KIF11 was also related to lymph node metastasis(N staging) in patients with lung cancer. In tumor-bearing models of lung cancer nude mice, compared with Control group, volume and weight of tumors, and positive expression of Ki67 were significantly decreased in PEL group(P<0.05). Compared with Control group, activities of NCI-H1975 and NCI-H292 cells, migration ability and number of invasion cells were significantly decreased in PEL group(P<0.05). Compared with negative control of miscellaneous short hairpin RNA(shNC) group, KIF11 expression, cells activity, migration ability and number of invasion cells were significantly decreased in shKIF11 1# group and shKIF11 2# group(P<0.05). Compared with PEL group, KIF11 expression, cells activity, migration ability and number of invasion cells were significantly increased in PEL+KIF11 group(P<0.05). Conclusion PEL can inhibit the proliferation, migration and invasion of lung cancer cells,and its mechanism of action may be related to inhibiting KIF11 expression.
作者
靳彩玲
姬颖华
王荦楠
杨军
张清琴
牛红蕊
JIN Cailing;JI Yinghua;WANG Luonan;YANG Jun;ZHANG Qingqin;NIU Hongrui(Department of Oncology,The First Affiliated Hospital of Xinxiang Medical College,Xinxiang 453000,China)
出处
《广东药科大学学报》
CAS
2021年第6期63-70,共8页
Journal of Guangdong Pharmaceutical University
基金
河南省医学科技攻关计划项目(2019050116)。
作者简介
靳彩玲(1978-),女,硕士,主任医师,主要从事肺癌基础与临床研究,Email:jding24428@sina.com。
