17AAG-Cypate聚合物胶束对A549细胞裸鼠移植瘤抑瘤效果的体内实验研究

Inhibitory effect of 17AAG-cypate polymer micelles on A549 cell xenografts in nude mice in vivo

目的研究17AAG-cypate胶束对肺腺癌A549细胞裸鼠移植瘤的抑制作用,并探讨其作用机制.方法用肺腺癌A549细胞建立裸鼠皮下移植瘤模型,分别给予生理盐水(生理盐水组)、射线照射(X-Ray)、17AAG胶束+射线照射(17AAG-M/X)、17AAG-Cypate胶束+激光/射线照射(17AAG-Cypate-M/L+X)处理.定期测量移植瘤大小,绘制移植瘤生长曲线;采用免疫组化法检测肿瘤组织增殖细胞核抗原(PCNA)和微血管密度表达;TUNEL法观察肿瘤细胞凋亡;蛋白印迹法检测肿瘤组织磷酸化ERK 1/2和磷酸化AKT的表达水平.结果与生理盐水组相比,X-Ray组、17AAG-M/X-Ray组、17AAG-Cypate-M/L+X组移植瘤生长均受到抑制,以17AAG-Cypate胶束组最为明显(P<0.05);各实验组肿瘤组织中PCNA蛋白表达水平明显下调(P<0.05),微血管密度也明显下调(P<0.05),磷酸化ERK 1/2和磷酸化AKT的表达量显著下降.结论17AAG-Cypate胶束可以抑制裸鼠体内非小细胞肺癌的生长,其机制可能是通过降低p-ERK 1/2和p-AKT的活性,从而减弱MAPK-ERK和PI3K-AKT信号通路的激活.

Objective To investigate the inhibitory effect of 17AAG-Cypate micelles on the non-small cell lung cancer A549 cells in nude mice and to explore its possible mechanism.Methods A549 lung adenocarcinoma tumor-bearing nude mice were established.The nude mice were treated with saline(saline group),X-ray(X-ray group),17AAG micelles+X-ray(17AAG-M/X group)and 17AAG-Cypate micelles+laser/X-ray(17AAG-Cypate-M/L+X group),respectively.The growth of xenograft tumors in different groups was measured on a regular basis to delineate the growth curve.The expression of proliferating cell nuclear antigen(PCNA)was measured by immunohistochemistry.The microvascular density was detected.The apoptosis of xenograft tissues was observed by TUNEL staining.The expression levels of p-ERK 1/2 and p-AKT were quantitatively measured by Western blot.Results Compared with the saline group,varying degrees of inhibition of tumor growth were observed in the X-ray,17AAG-M/X-ray and 17AAG-Cypate-M/L+X groups,particularly in the 17AAG-Cypate-M/L+X group(all P<0.05).In all groups,the expression levels of PCNA were significantly down-regulated(all P<0.05),the microvascular density was remarkably reduced(all P<0.05)and theexpression levels of p-ERK 1/2 and p-AKT were considerably down-regulated(all P<0.05).Conclusions 17AAG-Cypate micelles can inhibit the growth of human non-small cell lung cancer in nude mice,probably by reducing the activity of p-ERK 1/2 and p-AKT,thereby weakening the activation of the MAPK-ERK and PI3K-AKT signaling pathways.