摘要
目的 探索胰腺癌细胞对 5 氟尿嘧啶 ( 5 FU)和健择产生获得性耐药的机制 ,分析这种耐药与凋亡的调控基因———bcl 2家族之间的关系。方法 5 FU和健择的细胞毒性作用通过磺酰罗丹明B蛋白染色法 (SRB)来检测 ,应用RNA酶保护分析法来检测化疗药物作用前后bcl 2家族mRNA表达水平。结果 5 FU和健择对 3株胰腺癌细胞均产生了细胞毒性作用 ,5 FU长期作用后 ,Capan 1细胞 5 0 %抑制浓度 (IC50 )上升了 2 .1倍 (P <0 .0 5 )。健择长期作用后 ,Capan 1细胞IC50 上升了 1.8倍 (P <0 .0 5 )。RNA酶保护分析结果提示 ,bcl xL 和mcl 1上调的细胞产生了获得性耐药。结论 化疗药物长期作用后 ,抑凋亡基因bcl xL 和mcl 1上调 ,胰腺癌细胞产生了获得性耐药。阻断这些抑凋亡基因的表达可能提高胰腺癌细胞对 5 FU和健择的敏感性 ,从而产生治疗作用。
Objective To investigate the mechanism of acquired resistance of pancreatic cancer cell to 5-FU and gemcitabine and to a nalyze its correlation with the expression of apoptosis-regulating genes. Methods The cytotoxic effects of 5-FU and gemcitabine in Panc-1,Mia-Paca-2 and Capan-1 pancreatic cancer cells were assessed and mRN A expression levels of pro-apoptotic and anti-apoptotic genes of the bcl-2 fa mily were detected using RNase protection assay.Results P ancreatic cancer cells displayed a wide range of sensitivity to 5-FU and gemcit abine.After recurrent treatment with 5-FU,the IC 50 values in Capan-1 cel ls were increased by 2.1 fold as compared to their parental cells.Following recu rrent treatment with gemcitabine,the IC 50 values in Capan-1 cells were ra ised significantly by 1.8 fold (P< 0.01).RNase protection assay showed a negative correlation between bcl-x L and mcl-1 mRNA expression levels and th e sensitivity to 5-FU and gemcitabine after 5-FU and gemcitabine treatment. Conclusion These findings reveal that the levels of bcl- x L and mcl-1 following recurrent exposure to 5-FU or gemcitabine are associa ted with resistance to these drugs.These findings suggest that the activation of anti-apoptotic genes after recurrent drug exposure contributes to the chemores istance of pancreatic cancer cells and that their blockage might enhance chemose nsitivity in pancreatic cancer.
出处
《中华实验外科杂志》
CAS
CSCD
北大核心
2003年第4期329-330,共2页
Chinese Journal of Experimental Surgery
