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目的:探讨蛙皮素受体拮抗剂RC-3095联合吉西他滨(gemcitabine,GEM)是否有协同拮抗人胰腺癌细胞CFPAC-1生长的作用。方法:采用CCK-8法检测不同浓度的RC-3095、GEM以及联合治疗对胰腺癌细胞体外增殖的影响;给予荷瘤裸鼠RC-3095(20μg/d)、GEM[15 mg/(kg·3 d)]以及两者联合治疗4周,观察移植瘤的体积和重量变化;采用Western印迹法检测干预后移植瘤组织中蛙皮素受体的表达变化,包括GRP-R、NMB-R和BRS-3。结果:在体外试验中,联合用药组展现出强大的肿瘤细胞增殖抑制效应。干预4周后发现,RC-3095或GEM都可显著降低移植瘤的体积和重量。联合组比任何单一用药组都能更显著地抑制CFPAC-1移植瘤的生长。Western印迹法显示,RC-3095组或GEM组均能降低移植瘤中GRP-R和BRS-3的蛋白质表达;联合用药组降低作用更明显。结论:RC-3095联合GEM能协同抑制人胰腺癌细胞CFPAC-1在体外和体内的生长发展。这种协同抑制的效果与GRP-R和(或)BRS-3表达下降有关。
AIM: To investigate whether gemcitabine (GEM), a bombesin receptor antagonist, can antagonize the growth of human pancreatic cancer cell line CFPAC-1. Methods: The effects of different concentrations of RC-3095, GEM and combination therapy on the proliferation of pancreatic cancer cells were detected by CCK-8 assay. The effects of RC-3095 (20μg / d), GEM [15 mg / 3 d)] and the combination of the two for 4 weeks to observe the volume and weight changes of the xenografts. Western blotting was used to detect the expression of bombesin receptors in the tumor tissue after intervention, including GRP-R, NMB-R and BRS-3. Results: In the in vitro experiments, the combination group showed a strong inhibitory effect on tumor cell proliferation. After 4 weeks of intervention, it was found that either RC-3095 or GEM significantly reduced the size and weight of the xenografts. The combination group inhibited the growth of CFPAC-1 xenograft more significantly than either single drug group. Western blotting showed that the protein expression of GRP-R and BRS-3 in xenograft tumor was decreased in RC-3095 group or GEM group, and the effect of combination therapy was more obvious. Conclusion: RC-3095 combined with GEM can synergistically inhibit the growth and development of human pancreatic cancer cell line CFPAC-1 in vitro and in vivo. The effect of this synergistic inhibition is related to the decreased expression of GRP-R and / or BRS-3.