PDGF受体酪氨酸激酶抑制剂在胰腺癌中是否有作用?

摘要

目的:探讨PDGF受体酪氨酸激酶抑制剂(STI571)在胰腺癌中的应用及机制.方法:应用MTT方法检测胰腺癌细胞的生长情况,应用FACS(PI染色及Annexin染色)分析胰腺癌细胞的周期改变、凋亡发生及细胞的死亡机制.应用Western blot检测MAPK磷酸化与生长因子受体磷酸化水平.结果:STI571在胰腺癌中的GI50是17～31.5μmol·L-1,EGF、FGF-2与IGF-1均可刺激胰腺癌细胞的生长,STI571仅能部分阻断生长因子的作用.STI571对MAPK与生长因子受体磷酸化并无影响,对细胞周期亦无影响.结论:STI571对胰腺癌细胞的生长抑制作用不是通过酪氨酸激酶受体途径实现的,其具体机制及临床应用尚待进一步研究.%To investigate the potential role of STI571 in pancreatic cancer.Methods The GI50 of STI571 and the effects of STI571 on growth factor actions in pancreatic cell lines were analyzed by the MTT assay. FACS analysis using Annexin and PI staining was carried out to study cell cycle,apoptosis,and cell death. Western blot analysis was taken to measure MAP kinase and receptor tyrosine kinase phosphorylation. Results STI571 inhibited cell proliferation in pancreatic cancer cell lines with GI50 concentrations ranging from 17 to 31.5-μmol·L-1.EGF,IGF1,and FGF-2 other than PDGF exerted growth stimulatory effects in pancreatic cancer cell lines. STI571 only partialy blocked these effects on cell growth,and did not abrogate the phosphorylation of both growth factor-induced receptor and MAPK. Conclusion Our data demonstrate that STI571 inhibits pancreatic cancer cell growth with high GI50 concentrations through tyrosine-kinase receptor independent pathways.