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.

[1] JEMAL A, TIWARI R C, MURRAY T. American cancer society.Cancer statistics,2004, 2004(1)
[2] NEOPTOLEMOS J P, STOCKEN D D, FRIESS H. A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer. 2004(12). doi:10.1056/NEJMoa032295
[3] KORC M. Role of growth factors in pancreatic cancer, 1998
[4] EBERT M, YOKOYAMA M, FRIESS H. Induction of platelet-derived growth faoctor A and B chains and over-expression of their receptors in human pancreatic cancer. 1995. doi:10.1002/ijc.2910620507
[5] McGARY E C, WEBER K, MILLS L. Inhibition of platelet-derived growth factor-mediated proliferation of osteosarcoma cells by the novel tyrosine kinase inhibitor STI571. 2002
[6] OKUDA K, WEISBERG E, GILLILAND D G. ARG tyrosine kinase activity is inhibited by STI571. 2001
[7] DRUKER B J, TAMURA S, BUCHDUNGER E. Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr-Abl positive cells. 1996. doi:10.1038/nm0596-561
[8] CARROLL M, OHNO-JONES S, TAMURA S. CGP 57148,a tyrosine kinase inhibitor,inhibits the growth of cells expressing BCR-ABL,TEL-ABL,and TEL-PDGFR fusion proteinss, 1997
[9] TORRISANI J, BUSCAIL L. Molecular pathways of pancreatic carcinogenesis, 2002
[10] DRUKER B J, TALPAZ M, RESTA D J. Effcacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. 2001(14). doi:10.1056/NEJM200104053441401
[11] SJOBLOM T, SHIMIZU A, O'BRIEN K P. Growth inhibition of dermatofibrosarcoma protuberans tumors by the platelet-derived growth factor receptor antagonist STI571 through induction of apoptosis. 2001