论文部分内容阅读
用耐顺铂（ＣＤＤＰ）人肺腺癌细胞系Ａ５４９ＤＤＰ作模型，研究了５－ＦＵ对ＣＤＤＰ耐药的程序依赖性逆转作用。５－氟脲嘧啶（５－ＦＵ）预处理Ａ５４９ＤＤＰ２４ｈ后立即给予ＣＤＤＰ，ＣＤＤＰ细胞毒性增加３．９倍；５－ＦＵ预处理Ａ５４９ＤＤＰ后间隔２４或４８ｈ再给予ＣＤＤＰ，其细胞毒性分别增加２０倍和２５０倍，甚至较亲代细胞Ａ５４９更为敏感；如先给ＣＤＤＰ后给５－ＦＵ则细胞毒性仅增加１．８倍。５－ＦＵ对亲代细胞亦有类似效应但细胞毒性增加程度明显低于耐药细胞。５－ＦＵ预处理后间隔２４，４８ｈ，细胞内ＧＳＨ含量逐渐降低，与细胞毒性逐渐增加相一致。如用ＢＳＯ耗竭Ａ５４９ＤＤＰ细胞内ＧＳＨ，ＣＤＤＰ细胞毒性增加６．４倍，仅能部分逆转ＣＤＤＰ耐药。５－ＦＵ明显抑制ＭＲＰ的表达，但对ＧＳＴπ的表达无影响。在５－ＦＵ预处理后的无药间隔时间内，给予无毒浓度的三苯氧胺则有明显的协同效应。结论：程序性给予５－ＦＵ通过降低细胞内ＧＳＨ含量和抑制ＭＲＰ的表达能完全逆转ＣＤＤＰ耐药
Using a CDDP-resistant human lung adenocarcinoma cell line A549DDP as a model, the program-dependent reversal effect of 5-FU on CDDP resistance was studied. CDDP was administered immediately after pretreatment of A549DDP with 5-fluorouracil (5-FU) for 24h, and the CDDP cytotoxicity was increased 3.9-fold; 5-FU was pretreated with CDDP 24 or 48h after A549DDP pretreatment, and its cytotoxicity was increased by 20-fold and At 250-fold, it is even more sensitive than parental cell A549; if CDDF is given to 5-FU first, cytotoxicity increases only 1.8-fold. 5-FU also had similar effects on parental cells but the degree of cytotoxicity was significantly lower than that of resistant cells. At 24 and 48 h after 5-FU pretreatment, the intracellular GSH content gradually decreased, which was consistent with the gradual increase of cytotoxicity. If BSO is used to deplete intracellular GSH of A549DDP, the cytotoxicity of CDDP increases by 6.4 times, and it only partially reverses CDDP resistance. 5-FU significantly inhibited the expression of MRP, but had no effect on the expression of GSTπ. In the non-drug interval after 5-FU pretreatment, there was a significant synergistic effect when non-toxic tamoxifen was given. CONCLUSIONS: Programmed administration of 5-FU can completely reverse CDDP resistance by reducing intracellular GSH content and inhibiting MRP expression.