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目的:应用EP4受体拮抗剂ONO-AE3-208作用于裸鼠前列腺癌骨转移模型,观察其对前列腺癌骨转移形成的抑制作用。方法:将荧光素稳定转染前列腺癌PC3细胞构建PC3/LUC细胞,经小鼠左心室注射PC3/LUC细胞以构建全身转移模型。于构建术前1周开始按实验组及对照组分别给予ONO-AE3-208及双蒸水,应用活体生物发光成像系统观察术后两组小鼠模型转移形成时间、肿瘤荧光负荷及生存曲线的变化情况。结果:模型构建术后30d通过活体生物成像系统进行荧光负荷量的分析可见经双蒸水腹腔注射的对照组肿瘤负荷升高水平明显高于经ONO-AE3-208处理的实验组,且其升高水平与处理时间呈正比(P<0.01);对照组小鼠转移形成率(93.3%)显著高于实验组(33.3%)(P<0.01)。其中实验组的中位转移形成时间为29 d(95%CI=26.547~35.262),对照组仅有21 d(P<0.01),经ONO-AE3-208作用可以显著延长小鼠前列腺癌转移形成时间。结论:EP4受体拮抗剂ONO-AE3-208对小鼠前列腺癌骨转移的形成有抑制作用。
OBJECTIVE: To investigate the inhibitory effect of ONO-AE3-208, an EP4 receptor antagonist, on the bone metastasis of prostate cancer in nude mice. Methods: PC3 / LUC cells were stably transfected with PC3 cells by fluorescein and PC3 / LUC cells were injected into the left ventricle to construct a systemic metastasis model. One week before the operation, ONO-AE3-208 and double distilled water were given to the experimental group and the control group respectively. The bioluminescence imaging system was used to observe the time of metastasis, the fluorescence load and the survival curve of the two groups Changes. Results: The results of fluorescence load analysis by living biological imaging system 30 days after model construction showed that the tumor burden in control group injected with double distilled water was significantly higher than that in ONO-AE3-208 treated group, (P <0.01). The rate of metastasis in the control group (93.3%) was significantly higher than that in the experimental group (33.3%) (P <0.01). The median metastasis time was 29 days (95% CI = 26.547-35.262) in the experimental group and 21 days in the control group (P <0.01). The ONO-AE3-208 treatment significantly prolonged the metastasis of the prostate cancer in mice time. Conclusion: EPO receptor antagonist ONO-AE3-208 can inhibit the formation of bone metastasis in prostate cancer mice.