法米替尼在胃癌细胞MKN-45移植瘤中的作用

发布时间：2018-06-28 06:14

本文选题：胃癌 + MKN-细胞　；参考：《医学综述》2016年24期

【摘要】：目的探讨法米替尼在胃癌细胞MKN-45移植瘤中的作用。方法胃癌细胞MKN-45移植瘤裸鼠共20只按随机数字法分为对照组、法米替尼50 mg/kg组、法米替尼100 mg/kg组、法米替尼500 mg/kg组,5只/组,分别给予0.9%氯化钠注射液和50、100、500 mg/kg法米替尼;每日1次,连续22 d,口服给药。筛选出高效低毒剂量(50 mg/kg)进行第2次动物实验,方法相同,MKN-45移植瘤裸鼠共40只随机分为8组(5只/组):对照组(0.9%氯化钠注射液,每日1次,连续18 d,口服给药);法米替尼组(50 mg/kg,每日1次,口服给药);5-氟尿嘧啶(5-FU)组(10 mg/kg和20 mg/kg组,隔天1次,腹腔注射);顺铂(DDP)组(3 mg/kg和6 mg/kg组,每周1次,腹腔注射);紫杉醇(PTX)组(10 mg/kg组,每周1次;以及20 mg/kg组:每周2次,每次10 mg/kg;腹腔注射),连续18 d。给药过程中,记录裸鼠生长状况、肿瘤体积、裸鼠体质量、结束后肿瘤组织称质量等用来计算肿瘤抑制率和死亡情况,进而评估药物疗效和安全性。通过免疫组织化学CD34染色检测法米替尼用药后肿瘤血管的变化。结果与对照组相比,法米替尼50 mg/kg组和法米替尼100 mg/kg组在给药第8天后裸鼠肿瘤体积明显生长减缓,用药22 d后,各组裸鼠肿瘤体积[对照组(2036±805)mm~3,法米替尼50 mg/kg组:(343±167)mm~3,法米替尼100 mg/kg组:(304±206)mm~3],差异有统计学意义(P0.05)。给药第14日开始至给药结束,法米替尼100 mg/kg组裸鼠体质量较对照组和法米替尼50 mg/kg组明显下降,而对照组和法米替尼50 mg/kg组裸鼠体质量比较差异无统计学意义(P0.05)。用药22 d后,各组裸鼠体质量:对照组(21.58±2.32)g,法米替尼50 mg/kg组:(18.78±1.41)g;法米替尼100 mg/kg组:(15.08±2.63)g。法米替尼50 mg/kg剂量将作为安全有效剂量继续第2次实验。第2次实验对比对照组和各化疗组,法米替尼用药后肿瘤体积和最终肿瘤质量均显著降低。法米替尼组抑瘤率为93.0%,远远高于其他单药组(5-FU组:10 mg/kg 16.6%,20 mg/kg组37.9%;DDP 3 mg/kg 54.3%,6 mg/kg 58.2%;PTX:10 mg/kg组22.9%,20 mg/kg组52.2%)。法米替尼组CD_(34)表达较对照组明显降低(法米替尼组CD_(34)~-;对照组CD_(34)~(++))。结论法米替尼较其他传统化疗药物对于胃癌有更好的抗肿瘤作用,为今后临床试验提供一定的理论支持。
[Abstract]:Objective to investigate the role of famitinib in transplanted tumor of gastric cancer cell line MKN-45. Methods A total of 20 nude mice with MKN-45 transplanted tumor were randomly divided into control group (50 mg/kg), famitinib (100 mg/kg) group and famitinib (500 mg/kg) group (n = 5). Each group was given 0.9% sodium chloride injection and 50100500 mg/kg famitinib respectively. Once a day for 22 days, oral administration. A total of 40 nude mice with the same MKN-45 transplanted tumor were randomly divided into 8 groups (5 mice / group): control group (0.9% sodium chloride injection, once a day). The famitinib group (50 mg / kg, once a day, oral administration), 5-FU group (10 mg/kg and 20 mg/kg group, intraperitoneal injection every other day), cisplatin (DDP) group (3 mg/kg and 6 mg/kg groups, once a week), Paclitaxel group (10 mg/kg group, once a week, and 20 mg/kg group: twice a week, 10 mg / kg; intraperitoneal injection) for 18 days. During the course of administration, the growth status, tumor volume, body mass and tumor tissue weight of nude mice were recorded to calculate the tumor inhibition rate and death rate, and then to evaluate the efficacy and safety of the drug. The changes of tumor blood vessels after farmitinib were detected by immunohistochemical CD 34 staining. Results compared with the control group, the tumor volume of the nude mice in the famitinib 50 mg/kg group and the famitinib 100 mg/kg group decreased significantly after 8 days of administration, and 22 days later. The tumor volume of nude mice in each group [control group (2036 卤805) mm ~ (-3), famitinib 50 mg/kg group: (343 卤16.7) mm ~ (3), famitinib 100 mg/kg group: (304 卤206) mm~3], the difference was statistically significant (P0.05). From the 14th day of administration to the end of administration, the body mass of nude mice in famitinib 100 mg/kg group was significantly lower than that in control group and famitinib 50 mg/kg group, but there was no significant difference in body mass between control group and famitinib 50 mg/kg group (P0.05). After 22 days of administration, the body weight of nude mice in each group was (21.58 卤2.32) g in the control group, (18.78 卤1.41) g in the famitinib 50 mg/kg group and (15.08 卤2.63) g in the famitinib 100 mg/kg group. The second trial will continue as a safe and effective dose of famitinib 50 mg/kg. In the second experiment, compared with the control group and each chemotherapy group, the tumor volume and the final tumor quality decreased significantly after farmitinib treatment. The tumor inhibition rate of famitinib group was 93.0, which was much higher than that of other monotherapy group (5-FU group: 10 mg/kg 16.6and 20 mg/kg group, 37.9% DDP 3 mg/kg 54.3cm) and 6 mg/kg 58.2%. PTX: 10 mg/kg group 22. 9% and 20 mg/kg group 52.2%. The expression of CD34 in the famitinib group was significantly lower than that in the control group (CD34) and CD34 ~ (). In the control group was significantly lower than that in the control group. Conclusion famitinib has better antitumor effect on gastric cancer than other traditional chemotherapeutic drugs, which provides some theoretical support for clinical trials in the future.
【作者单位】：浙江省肿瘤医院化疗科;北京大学肿瘤医院暨北京市肿瘤研究所消化肿瘤内科;
【分类号】：R96

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