胰腺癌细胞株对氟尿嘧啶存在固有不敏感性

Intrinsic Resistance of Pancreatic Cancer Cell Lines towards 5-Fluorouracil

目的 研究胰腺癌细胞株是否对氟尿嘧啶 ( 5 - FU )具有固有或获得性不敏感。方法 用 SRB方法检测5 - FU对胰腺癌细胞株 As PC- 1、Capan- 1、Mia- Pa Ca- 2、Panc- 1和 T3 M4的毒性作用。结果 5 - FU对所有胰腺癌细胞株的 IC50 都很高 ,其中 Mia- Pa Ca- 2和 Panc- 1细胞株对 5 - FU最不敏感 ( IC50 =12 ,13 nmol/ L )。即使是在 5 - FU最敏感的 Capan- 1细胞株 ,其 IC50 仍相当高 ( 473 pm ol/ L)。这些细胞株对 5 - FU的 IC50 甚至高出其临床常用剂量给药时血浆药物浓度的 1～ 5 6倍。结论 大多数胰腺癌细胞株对 5 - FU固有不敏感 ,这些发现也许能作为临床上 5 -

AIM To investigate whether the pancreatic cancer cells possess the intrinsic or acquired resistance to 5-fluorouracil(5-FU). METHODS The cytotoxic effects of 5-FU on AsPC-1, Capan-1, Mia-PaCa-2, Panc-1 and T3M4 pancreatic cancer cells were assessed by the sulforhodamine B protein assay (SRB). RESULTS The IC 50 of 5-FU in pancreatic cancer cell lines was exceedingly high. Panc-1 and Mia-PaCa-2 showed the highest resistance to 5-FU (IC 50= 12 and 13 μmol/L, respectively), and even in the most sensitive cell line, Capan-1, the IC 50 was still relatively high (473 pmol/L). These IC 50 were even much higher (1～56 times) than plasma concentrations when 5-FU was given to patients at a standard dosage. CONCLUSION Most of the pancreatic cancer cell lines are intrinsic resistant to 5-FU. These findings may represent one of the reasons why pancreatic cancer responds only poorly to 5-FU treatment in the clinical practice.