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目的本研究通过观察哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin,mTOR)抑制剂依维莫司对大鼠嗜铬细胞瘤裸鼠移植瘤生长的影响,探讨依维莫司对大鼠嗜铬细胞瘤肿瘤生长和血管生成的抑制作用。方法用大鼠嗜铬细胞瘤细胞PC12接种于裸鼠皮下,建立移植瘤模型,15d后将荷瘤裸鼠随机分为2组,每组12只,分别为实验组(依维莫司灌胃5mg/kg)和对照组(生理盐水灌胃10mL/kg),用药3周,第4周后测量裸鼠移植瘤的体积变化以及裸鼠的生存时间,采用免疫组化方法检测肿瘤组织中信号转导和转录活化因子3(signal transducers and activators of transcription 3,STAT3)、血管内皮生长因子(vascular endothelial growth factor,VEGF)的表达,采用Western blotting法检测肿瘤组织中STAT3、VEGF的表达。结果第4周时,对照组的移植瘤体积为(4340.67±794.07)mm3,实验组的移植瘤体积为(1 506.01±352.69)mm3,两组移植瘤体积存在显著统计学意义(P<0.05)。对照组的平均生存时间是(25.3±2.4)d,实验组的平均生存时间是(37.8±4.6)d,用KaplanMeier,Log-Rank方法分析两组的生存函数的差异有统计学意义(P<0.05)。实验组肿瘤组织的STAT 3,VEGF表达明显低于对照组(P<0.05)。结论依维莫司对大鼠嗜铬细胞瘤裸鼠移植瘤有明显抑制作用,并可降低肿瘤组织中STAT 3和VEGF的表达。
OBJECTIVE: To investigate the effect of everolimus, a mammalian target of rapamycin (mTOR), on the growth of xenografted rat pheochromocytoma xenografts in nude mice. Inhibition of tumor growth and angiogenesis in pheochromocytoma. Methods Rat pheochromocytoma cell line PC12 was inoculated subcutaneously in nude mice to establish a transplanted tumor model. After 15 days, nude mice bearing tumor were randomly divided into two groups (n = 12 each), which were experimental group 5mg / kg) and control group (saline 10mL / kg) for 3 weeks. After 4 weeks, the volume changes of xenografts in nude mice and the survival time of nude mice were measured. The signal of tumor tissue was detected by immunohistochemistry The expressions of STAT3 and VEGF were detected by Western blotting. The expressions of STAT3 and VEGF were detected by Western blotting. Results At 4 weeks, the volume of xenograft in the control group was (4340.67 ± 794.07) mm 3 and that in the experimental group was (1 506.01 ± 352.69) mm 3. There was significant difference between the two groups (P <0.05) . The mean survival time in the control group was (25.3 ± 2.4) days, and the mean survival time in the experimental group was (37.8 ± 4.6) days. There was significant difference in survival function between the two groups by Kaplan Meier and Log-Rank methods (P < 0.05). The expression of STAT3 and VEGF in the experimental group was significantly lower than that in the control group (P <0.05). Conclusion Everolimus significantly inhibited the transplanted tumor of nude mice with pheochromocytoma and decreased the expression of STAT3 and VEGF in tumor tissue.