Development of new therapy for hormone independent prostate cancer.

研究了FGFR2IIIb在激素非依赖性前列腺癌中对细胞增殖和分化的影响，以及FGFR2IIIb联合放射治疗和抗癌药物的作用。1)FGFR2IIIb转基因PC-3细胞的建立：PC-3FGFR2IIIb转基因细胞的生长速度明显慢于对照组。PC-3FGFR2IIIb来源的肿瘤生长速度明显慢于对照组。PC-3FGFR2IIIb细胞由PC-3neo细胞形态发生改变。免疫细胞化学显示对照组泛角蛋白和乳铁蛋白呈弱阳性染色，而PC-3 FGFR2IIIb细胞泛角蛋白和乳铁蛋白免疫染色呈强阳性。2)FGFR2IIIb的信号转导：FRS2在成纤维细胞生长因子-1刺激的PC-3neo和PC-3FGFR2IIIb细胞中均为酪氨酸磷酸化蛋白。PC-3FGFR2IIIb的FRS2信号强度明显强于对照组。在成纤维细胞生长因子-7的刺激下，FRS2在PC-3v细胞中被强烈激活，而在PC-3neo细胞中不被激活。在成纤维细胞生长因子-1和成纤维细胞生长因子-7的刺激下，p44/42 MAPK在PC-3FGFR2IIIb细胞中被检测到，而在PC-3neo细胞中未检测到。3)辐射和抗癌剂与FGFR2IIIb4和8Gy射线的协同作用使PC3-IIIb细胞的集落数分别减少了87.7%和99.6%。携带空载体的模拟细胞克隆数分别减少69.4%和95.2%。未加多西紫杉醇的PC-IIIb组、PC3-IIIb+0.01μM多西紫杉醇组和PC3-IIIb+0.1μM多西紫杉醇组第3天的平均细胞存活率分别为0.34、0.24和0.20。两组之间的差异具有统计学意义(p&lt；0.0001)。

The role of FGFR2IIIb in cell proliferation anddifferentiation were studied in hormone independentprostate cancer, and usefulness of combination therapyusing radiation and anticancer agent were also studied in the FGFR2IIIb transfected cell.1)Establishment of FGFR2IIIb transfected PC-3 cell :The growth rate of PC-3 FGFR2IIIb transfected cells was significantly slower than that of the control cells. The growth rate of the PC-3 FGFR2IIIb derived tumors was significantly slower than that of the control. PC-3 FGFR2IIIb cells were morphologically changed from PC-3 neo cells. Immunocytochemical analysis revealed a weak pancytokeratin and lactoferrin-positive staining of the control, whereas PC-3 FGFR2IIIb cells showed strong positive pancytokeratin and lactoferin immunostaining. In the apoptosis assay, most of PC-3 FGFR2IIIb cells were stained with the APOPercentage-dye.2)Signal transduction of FGFR2IIIb :FRS2 was identified as a tyrosine-phosphorylated protein in both PC-3 neo and PC-3 FGFR2IIIb cells stimulated with FGF-1. The signal intensity of FRS2 in PC-3 FGFR2IIIb was much stronger than that of the control. On the stimulation with FGF-7, FRS2 was strongly activated in PC-3 v cells but not in PC-3 neo cells. On stimulation with FGF-1 and FGF-7, the phosphorylation of p44/42 MAP kinase was detected in PC-3 FGFR2IIIb cells, but not in PC-3 neo cells.3)Synergistic effects of radiation and an anticancer agent with the FGFR2IIIbFour and 8 Gy of radiation treatment dramatically decreased the number of colonies in PC3-IIIb cells by 87.7 % and 99.6 %, respectively. The number of colonies in Mock cells bearing an empty vector was reduced by 69.4% and 95.2%, respectively. The mean cell viability on day 3 was 0.34 for PC-IIIb without docetaxel, 0.24 for PC3-IIIb1+0.01μM docetaxel, and 0.20 for PC3-IIIb + 0.1μM of docetaxel. The difference between the groups was statistically significant (p<0.0001).