促性腺激素释放激素论文：丙氨瑞林对人子宫内膜癌裸鼠皮下移植瘤的作用及其对PCNA的影响.docVIP

促性腺激素释放激素论文：丙氨瑞林对人子宫内膜癌裸鼠皮下移植瘤的作用及其对PCNA的影响 【中文摘要】探讨不同剂量促性腺激素释放激素类似物丙氨瑞林对人子宫内膜癌细胞株HEC-1B裸鼠皮下移植瘤的抑制作用，并探讨其可能的作用机制。方法：体外培养人子宫内膜癌细胞株HEC-1B，建立人子宫内膜癌裸鼠皮下移植瘤模型。造模成功3天后，将24只实验荷瘤裸鼠随机分为四组，6只／组，分别为生理盐水对照组、丙氨瑞林低剂量组、丙氨瑞林中剂量组、丙氨瑞林高剂量组。治疗组给予不同剂量的丙氨瑞林分别为15ug／kg、30ug／kg、60 ug／kg（资料显示丙氨瑞林应用于临床的剂量为200ug／d，依此按体重计算出应用于裸鼠的剂量约为30 ug／kg）。观察丙氨瑞林对子宫内膜癌细胞HEC-1B裸鼠皮下移植瘤的生长抑制情况；取裸鼠皮下移植瘤行HE染色，于光镜下观察肿瘤细胞的改变；采用免疫组化观察肿瘤细胞中PCNA基因的表达情况；实验完成后取裸鼠的心脏、肝脏、肾脏等重要脏器行HE染色，于光镜下观察丙氨瑞林的副作用。结果：经过4周治疗后，1、病理学观察对照组细胞密集，呈片状，有局灶性坏死，细胞有明显异型性，核大深染，可见核固缩、核溶解、核碎裂，染色质成团块状；2、各组移植瘤的体积分别为低剂量组1357 130mm~3，中剂量组1208 98 mm~3、高剂量组826 108 mm~3，与对照组1684 152 mm~3相比，有显著性差异（P0.01），治疗组的抑瘤率分别为低剂量组19.4%、中剂量组25.3%、高剂量组51.0%，且各两两组间比较差异有统计学意义（P0.01）；3、免疫组织化学检测结果：随着药物浓度的增加，PCNA的表达降低，且各组两两比较差异均有显著统计学意义（P﹤0.01）；4、在肿瘤生长及药物治疗过程中，裸鼠生长良好，活动正常。光镜下观察心脏、肝脏、肾脏HE染色结果未发现明显异常及副作用。结论：丙氨瑞林能抑制人子宫内膜癌裸鼠移植瘤的生长，且呈剂量依赖关系，其作用机制可能与下调PCNA的表达有关系。 【英文摘要】To study the anti-tumor effect and its mechanism of Alarelin at differentconcentration on human Endometrial carcinoma line HEC-1B implanted under the skin of nudemice in vivo.Methods Human endometrial carcinoma HEC-1-B cells were cultured in vitro.Nude micemode of transplanted human endometrial carcinoma was established by injecting HEC-1-B cellsinto subcutaneous of right lower limbs next groin,and after 3 days , twenty-four model nude micedivided into four groups randomly,which include the high dose Alarelin group、the middle doseAlarelin group、the low dose Alarelin group (the dose of Alarelin were 60ug／kg、30ug／kg、15ug／kg ) and blank control group(physiological saline). The status of growth inhabiting wasevaluated.The changes of xenograft morphology were observed by light microscopy with HEstaining.After treatment with Alarelin,the change of PCNA gene expressions were estimated byRT-PCR methods. Heart sections,liver sections and kidney sections were examined by HEstaining for assessment of toxicity.Results After 4 weeks of treatment(1)The blank control group in pathological observation showed cells became platy densely