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紫铆素经EGFR-STAT3信号通路对荷宫颈癌裸鼠肿瘤生长的影响

Effect of butin on the growth of cervical carcinoma in nude mice via EGFR-STAT3 signaling pathway
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摘要 目的探讨紫铆素对荷宫颈癌裸鼠肿瘤生长与肿瘤组织表皮生长因子受体(EGFR)、信号转导和转录激活因子3(signal transducer and activator of ranscription 3,STAT3)表达的影响。方法裸鼠左侧腑下接种宫颈癌SiHa细胞的方法构建宫颈癌模型,将成功构建的荷宫颈癌裸鼠随机分为模型组、阳性药组与低、中、高剂量组,每组各12只。低、中、高剂量组裸鼠分别给予11.5 mg/ml、46 mg/ml、115 mg/ml注射剂量的紫铆素注射,阳性药组给予4.3 ml/kg剂量的顺铂注射,模型组给予等量生理盐水;每天1次,连续注射7 d后,观察1周。测定各组裸鼠的抑瘤率及肝脏指数、肾脏指数;HE染色形态学观察肿瘤的病理特点,免疫组化、RT-qPCR检测肿瘤组织中EGFR、STAT3的表达水平。结果抑瘤率分析阳性药组(60.82±7.30%)和高剂量组(49.30±10.42)高于低、中剂量组,肿瘤体积与瘤重低于低、中剂量组和模型组;肾脏指数分析阳性药组(10.25±0.48)和高剂量组(10.13±0.47)低于模型组和低、中剂量组;EGFR蛋白表达阳性药组(0.002±0.002)、高剂量组(0.012±0.008)和STAT3蛋白表达阳性药组(0.063±0.011)、高剂量组(0.099±0.013)显著低于模型组和低、中剂量组;EGFR基因表达阳性药组(0.462±0.092)、高剂量组(0.524±0.115)和STAT3蛋白相对表达量阳性药组(0.435±0.123)、高剂量组(0.593±0.092)显著低于模型组和低、中剂量组;病理特点显示阳性药组、高剂量组肿瘤组织坏死情况较模型组和低、中剂量组明显降低;以上指标,差异有统计学意义(P<0.05)。结论紫铆素可有效抑制宫颈肿瘤的生长,且无明显毒性作用,其机制可能与宫颈肿瘤组织EGFR、STAT3表达相关。 Objective To investigate the effect of butin on tumor growth and expression of EGFR receptor(EGFR),signal transducer and activator of transcription 3(STAT3)in nude mice with cervical cancer.Methods Cervical carcinoma model was established by inoculating Si Ha cells into the left side of subabdomen in nude mice.The nude mice bearing cervical carcinoma were randomly divided into model group,positive drug group,low,medium and high dose groups,with 12 mice in each group.The nude mice in the low,medium and high dose groups were injected with 11.5 mg/ml,46 mg/ml and 115 mg/ml of butin respectively.The positive drug group was injected with 4.3 ml/kg of cisplatin,and the model group was injected with the same amount of normal saline once a day for 7days and then observed for 1 week.The tumor inhibition rate,liver index and kidney index were measured.HE staining was used to observe the pathological characteristics of tumor,and the expression levels of EGFR and STAT3 in the tumor tissues were detected by immunohistochemistry and RT-qPCR methods.Results Tumor inhibition rate in the positive drug group(60.82±7.30%)and the high dose group(49.30±10.42)were higher than those in low and medium dose groups,and tumor volume and weight were lower than those of low and medium dose group and model group.Renal index of the positive drug group(10.25±0.48)and the high dose group(10.13±0.47)were lower than that of the model group and the low and medium dose group.Expression of EGFR(0.002±0.002),STAT3(0.063±0.011),high dose(0.099±0.013)and high dose(0.012±0.008)groups were significantly lower than those of model group,low and medium dose group.The expression of EGFR(0.462±0.092),STAT3(0.435±0.123)and STAT3(0.593±0.092)in high-dose group were significantly lower than those in model group,low-dose group and medium-dose group.The pathological characteristics showed that the necrosis of tumor tissue in positive drug group and high dose group was significantly lower than those in model group and low and medium dose group(P<0.05).Conclusion Butin can effectively inhibit the growth of cervical cancer without obvious toxic effect,and its mechanism may be related to the expression of EGFR and STAT3 in cervical cancer tissues.
作者 徐佩风 韩莉莉 XU Peifeng;HAN Lili(Department of Gynecology,people's Hospital of Xinjiang Uygur Autonomous Region,Urumqi,830001,China)
出处 《新疆医学》 2023年第9期1040-1043,1048,共5页 Xinjiang Medical Journal
基金 国家自然科学基金地区项目(项目编号:82060296)
关键词 宫颈癌 紫铆素 抑瘤率 肿瘤生长 EGFR-STAT3信号通路 Cervical cancer Butin Tumor inhibition rate Tumor growth EGFR-STAT3 signaling pathway
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