胰腺癌耐吉西他滨细胞株的构建和转移能力的研究

Construction and metastasis ability of gemcitabine resistant cell line in pancreatic cancer

目的构建BxPC3胰腺癌耐吉西他滨细胞株模型,并探索其转移能力的变化。方法利用低剂量持续诱导的方法构建胰腺癌吉西他滨耐药细胞株BxPC3-GR,通过转录组学测序分析吉西他滨敏感细胞株和吉西他滨耐药细胞株的差异基因表达情况;GO富集分析探讨吉西他滨耐药细胞株差异基因参与的信号通路;Trans-well小室迁移实验检测耐药后胰腺癌细胞株的转移能力变化,并检测上皮间质转化特异性标志物变化情况。结果与敏感细胞株BxPC3-GS相比,吉西他滨对耐药细胞株BxPC3-GR的抑制率更低,更易发生迁移。而且代表细胞间质转化属性的标志物表达明显升高,代表上皮性质的标志物表达下降;耐药细胞株BxPC3-GR与敏感细胞株BxPC3-GS之间存在明显的差异表达基因。结论与吉西他滨敏感细胞株BxPC3-GS比较,吉西他滨耐药细胞株BxPC3-GR具有更强的转移能力。

Objective To construct BxPC3 pancreatic cancer cell line resistant to Gemcitabine and explore the changes of its metastatic ability.Method The Gemcitabine resistant cell line BxPC3-GR was constructed by continuous induction at low dose,and the differential gene expression between Gemcitabine sensitive cell line and Gemcitabine resistant cell line was analyzed by transcriptome sequencing.GO enrichment analysis was used to explore the signal pathway involved in the differential genes of Gemcitabine resistant cell lines,Trans-well chamber test was used to detect the changes of metastasis ability of pancreatic cancer cell lines after drug resistance,and the changes of EMT specific markers were detected.Result BxPC3-GR cell line is less sensitive to Gemcitabine treatment than BxPC3-GS cell line,and there were significant differentially expressed genes between BxPC3-GR and BxPC3-GS.BxPC3-GR cell line was more likely to migrate than BxPC3-GS cell line,and the expression of markers of epithelialmesenchymal transformation was significantly increased.Conclusion Compared with Gemcitabine sensitive pancreatic cancer cell line BxPC3-GS,Gemcitabine resistant pancreatic cancer cell line BxPC3-GR has stronger metastatic ability.