雷帕霉素抑制子宫内膜癌裸鼠移植瘤生长活体成像的观察

Bioluminescence imaging evaluation of the inhibitory effect of rapamycin in nude mice bearing endometrial cancer cell lines

目的:观察雷帕霉素(RA-PA)对不同PTEN表达子宫内膜癌裸鼠移植瘤的抑制作用。方法:通过慢病毒转染构建稳定表达绿色荧光蛋白(GFP)的HEC-1A(PTEN阳性)和Ishikawa(PTEN阴性)细胞株,建立裸鼠移植瘤模型。活体成像系统观察肿瘤的生长情况。观察RAPA治疗后肿瘤的体积及重量的变化。HE染色观察肿瘤的病理形态学变化。结果:建立稳定表达GFP的子宫内膜癌细胞系及裸鼠移植瘤模型,活体荧光成像显示,治疗组裸鼠荧光强度较对照组明显减弱。治疗组肿瘤体积及重量明显小于对照组(P<0.05),Ishikawa细胞组的抑瘤率(67.1%)较高于HEC-1A细胞组的抑瘤率(48.1%)。治疗组的肿瘤组织可见大片肿瘤细胞坏死,对照组肿瘤细胞坏死少。结论:RAPA对PTEN阳性及阴性的子宫内膜癌生长均有明显的抑制作用,PTEN的丢失可增加RAPA抗子宫内膜癌的敏感性。

OBJECTIVE： To investigate the inhibitory effect of rapamycin（RAPA） in nude mice bearing endometrial cancer cell lines with different PTEN status.METHODS： HEC-1A（PTEN positive） and Ishikawa（PTEN negative） cell lines with stable expression of green fluorescent protein（GFP） were established by transfection via lentiviral vector.The HEC-1A-GFP and Ishikawa-GFP cells were inoculated into the nude mice to prepare the subcutaneously xenografted tumor model.The dynamic growth of xenografted tumor was observed using fluorescence imaging system in vivo.After treated with RAPA,the volume and weight of transplanted tumors in nude mice were measured.Morphology of transplanted tumor tissues was observed by HE staining.RESULTS： The stable GFP-expressing endometrial cancer cell lines and xenografted tumor model were obtained.Optical imaging showed that the fluorescent intensity of treated group was apparently lower than that of the control.As compare with control group,the tumor volume and weight of treated group were significantly decreased（P0.05）.The inhibition rates of treated group inoculated with HEC-1A cell line was 48.1%,and that of treated group inoculated with Ishikawa cell line was 67.1%.Rapamycin treated groups induced obvious necrosis of tumor cells in implanted tumor tissues.CONCLUSION： Rapamycin shows potent anti-tumor activity in endometrial transplanted tumor independent of PTEN stutas,and the sensitivity of endometrial tumor to rapamycinis enhanced when loss of PTEN.