夫拉平度对人宫颈癌CasKi细胞裸鼠皮下种植瘤生长的抑制作用研究

周焕芹

[摘要] 目的 研究周期蛋白激酶（CDKs）抑制劑夫拉平度（Flavopiridol， FP）对人宫颈癌CasKi细胞裸鼠皮下移植瘤生长和转移的影响。方法 2017年7—8月在聊城市人民医院中心实验室建立CasKi细胞裸鼠模型，随机分为对照组、顺铂组、FP组及FP和顺铂联合用药组，每组8只裸鼠，4组均于肿瘤抑制成功后瘤体直径平均为0.8 cm开始给药，给药3周，2次/周。最后一次给药5 d后处死全部裸鼠，测量移植瘤的体积和重量，采用免疫印迹法检测对各组中肿瘤组织凋亡蛋白Caspase 3表达的影响，并采用分光光度法测定裸鼠血清超氧化物歧化酶（SOD）、丙二醛（MDA）水平。结果 与对照组相比[（567.02±89.38）V/mm3；（0.63±0.07）m/g]，顺铂组[（114.50±18.07）V/mm3，（0.12±0.04）m/g]、FP组[（106.74±21.39）V/mm3；（0.10±0.02）m/g]及FP和顺铂联合用药组[（88.59±19.84）V/mm3，（0.07±0.02）m/g]荷瘤体积和重量明显减小（P<0.05）；顺铂组、FP组及FP和顺铂联合用药组Caspase 3表达均显著增加（P<0.05）；与对照组相比[（134.68±45.63）U/mL，（3.45±1.47）mmol/L]，顺铂组[（143.72±44.45）U/mL，（2.76±2.83）mmol/L]、FP组[（156.51±32.53）U/mL，（2.64±0.66）mmol/L]及FP和顺铂联合用药组[（208.37±63.35）U/mL，（2.38±1.13）mmol/L]血清SOD的活性显著升高（P< 0.05），MDA的含量显著降低（P< 0.05）。结论 夫拉平度对人宫颈癌CasKi细胞皮下种植瘤生长具有抑制作用，且与促进癌细胞的凋亡，抑制机体氧化应激反应有关。

[关键词] 夫拉平度；顺铂；宫颈癌；生长抑制；凋亡； 氧化应激

[中图分类号] R73 [文献标识码] A [文章编号] 1674-0742（2018）04（c）-0018-04

Research on Inhibition Effect of Flavopiridol on the Growth of in Human Cervical Carcinoma CasKi Subcutaneous Implanted in Nude Mice

ZHOU Huan-qin

Department of Pharmacy， Liaocheng Peoples Hospital， Liaocheng， Shandong Province， 252000 China

[Abstract] Objective To study the effect of flavopiridol （FP） on human cervical carcinoma subcutaneous implanted tumor growth inhibition in mice bearing CasKi cell. Methods The nude rat model of cervical cancer cell was established from July to August 2017 in Central laboratory of Liaocheng Peoples Hospital. The nude rat were randomly divided into four groups （control group， cisplatin group， FP group and combined treatment group， 8 rats in each group）， and the four groups were administered when the average tumor diameter was 0.8 cm， 3 w， and 2 times/w， and all the mice were sacrificed in 5 days after the adminitration， and the volume and weight of tumors were tested. And the expression of caspase3 was determined by immunoblotting. And the SOD and MDA levels were measured by the spectrophotometry. Results The tumor volume and weight obviously decreased in the cisplatin group[（114.50±18.07）V/mm3；（0.12±0.04）m/g]， FP group[（106.74±21.39）V/mm3； （0.10±0.02）m/g] and combined treatment group[（88.59±19.84）V/mm3；（0.07±0.02）m/g]（P<0.05） compared with that in the control group[（567.02±89.38）V/mm3；（0.63±0.07）m/g）]， and the expression of caspase 3 in the cisplatin group， FP group and combined treatment group obviously increased compared with that in the control group [（134.68±45.63）U/mL，（3.45±1.47）mmol/L]. The activition of serum SOD in the cisplatin group[（143.72±44.45）U/mL，（2.76 ±2.83）mmol/L]， FP group[（156.51±32.53）U/mL，（2.64±0.66）mmol/L] and combined treatment group[（208.37±63.35）U/mL，（2.38±1.13）mmol/L] obviously increased （P<0.05）， the contents of MDA obviously decreased （P<0.05）. Conclusion FP has an inhibition effect on the growth of in human cervical carcinoma CasKi subcutaneous implanted in nude mice， which is related to promoting the apoptosis of cancer cells and inhibiting the oxidative stress reaction of the body.

[Key words] Flavopiridol； Cisplatin； Cervical carcinoma； Growth inhibition； Apoptosis； Oxidative stress

宫颈癌是危害女性健康常见的恶性肿瘤之一，其发病率较高，在发展中国家妇女中其发病率居第一位，且近年来宫颈癌发病率上升趋势明显[1-2]。因此，寻找治疗宫颈癌的有效方法是目前的研究热点之一。早期宫颈癌治疗后患者5年生存率较高，然而对于中晚期宫颈癌患者，易出现周围组织肿瘤转移，手术和放疗均难取得满意的治疗效果。因此，化疗在宫颈癌治疗中日益受到重视，然而目前化疗药物均存在不良反应大、久用易产生耐药性等缺点，因此寻找选择性高、不良反应小而有效的宫颈癌治疗药物尤为重要。夫拉平度（Flavopiridol， FP）为周期蛋白激酶（CDKs）抑制剂，通过降低肿瘤细胞内紊乱的CDK激酶活性，可以抑制人白血病细胞、食道和胃癌及乳腺癌细胞的增殖[3-4]。……