Tau基因表达与紫杉醇治疗胃癌敏感性的研究

目的:探讨胃癌细胞的Tau基因表达丰度与紫杉醇治疗敏感性间的关系,并分析其可能的耐药机制。方法:通过实时定量PCR筛选出Tau基因高表达和低表达的胃癌细胞株各一,然后观察两细胞株对紫杉醇的反应;并应用细胞增殖实验(CCK8方法)、流式细胞技术(AnnexinⅤ标记)检测紫杉醇在体外对胃癌细胞增殖、凋亡和周期的影响。对于Tau基因高表达的胃癌细胞,通过小干扰RNA(small interfering RNA,siRNA)等技术,观察其敲低Tau基因表达后,对紫杉醇的敏感性有无变化。结果:体外增殖实验显示,紫杉醇对Tau表达低的胃癌细胞的增殖生长抑制作用更为明显(P0.05)。而体外凋亡实验显示,紫杉醇更能促进Tau基因低表达胃癌细胞的凋亡(P0.05),在整个细胞周期中以G2/M期为主。而应用siRNA技术将Tau基因高表达的胃癌细胞降为低基因表达后,紫杉醇对其增殖的抑制作用明显增高(P0.05),更能促进转染后细胞的凋亡(P0.05);且对整个细胞周期,以作用于G2/M期为主。结论:紫杉醇对Tau基因表达低的胃癌细胞具有更强的增殖抑制作用,且更能促进其凋亡。而对干扰后的胃癌细胞,紫杉醇具有更强的抑制增殖作用,且更能促进其凋亡。

Sensitivity research on Tau gene expression and the use of paclitaxel in the treatment of gastric cancer

Objective To investigate the effective relationship between gastric cancer cell lines with different Tau gene expression and their treatment sensitivity to paclitaxel,and possible drug-resistance mechanisms.Methods One cell line with high Tau gene expression and another cell line with lower Tau gene expression were used,and their response to paclitaxel treatment were screened by real time fluorescence quantitative PCR among a total of 10 gastric cancer cell lines.The influence to the proliferation,apoptosis and cell cycle of these two cell lines were evaluated by CCK-8 kit and Annexin-Ⅴ＋PI.To the cell line having the higher Tau gene expression,we tried to knock it down by siRNA,and watched the change in sensitivity to paclitaxel treatment.Results The status of cell proliferation in vitro showed that paclitaxel produced an obvious inhibition effect on the gastric cancer cell proliferation which possessed the lower Tau gene expression（P〈0.05）.In vitro experiments also showed that paclitaxel could also promote apoptosis on low Tau gene expression gastric cancer cell line（P〈0.05）.Cell cycles were mainly effected on the G2 stage.Application of siRNA technology showed that after reduction in expression of Tau gene expression,paclitaxel significantly increased the state of proliferation in the cell line（P〈0.05）,and promoted their apoptosis（P〈0.05）.Conclusions Paclitaxel has a stronger inhibitory effect on proliferation in the low Tau gene expression gastric cancer cell line,and can promote apoptosis on these cells.As to the gastric cancer cells having experienced knock-down in Tau gene expression,paclitaxel can both increase their proliferation and promote their apoptosis.