雷替曲塞对人胃癌细胞MGC-803裸鼠移植瘤的抑制作用

 目的 通过研究雷替曲塞抑制裸鼠MGC-803胃癌移植瘤的生长,初步探讨其相关作用机制。方法 建立人胃癌裸鼠皮下移植瘤模型,把24只裸鼠随机分为3 组,每组8只。对照组(生理盐水),低剂量组(雷替曲塞5 mg/kg),高剂量组(雷替曲塞12 mg/kg)。每周经腹腔注射给药2次,持续2周。详细记录裸鼠精神状态、体重以及肿瘤生长情况,免疫组化法检测裸鼠肿瘤组织Ki67及PCNA蛋白表达,并通过Western blottting法检测裸鼠肿瘤组织Caspase-3及Bax蛋白表达。结果 治疗期间雷替曲塞低剂量组和高剂量组裸鼠体重均低于对照组,低剂量组、高剂量组的抑瘤率分别为27.54%、44.20%,差异有统计学意义(P<0.05);免疫组化法显示低剂量组、高剂量组Ki67阳性细胞率分别为58.95%、42.16%,PCNA阳性细胞率分别为51.36%、37.27%,均明显低于对照组(P<0.05);Western blotting法表明低剂量组、高剂量组Caspase-3和Bax蛋白表达均明显高于对照组(P<0.05)。结论 雷替曲塞可抑制人胃癌裸鼠移植瘤的生长增殖,其机制可能与提高Caspase-3和Bax蛋白表达、从而促进细胞凋亡有关。

Inhibitory effect of raltitrexed on MGC-803 human gastric cancer xenografts in nude mice

Objective To investigate the inhibitive effect of raltitrexed on MGC-803 human gastric cancer xenografts in nude mice, and to explore the mechanisms tentatively.Methods Models of human gastric cancer in nude mice were established by subcutaneous transplantation before 24 mice were randomly assigned into three groups: control group (normal saline),low-dose group (raltitrexed, 5 mg/kg) and high-dose group (raltitrexed, 12 mg/kg). Drugs were injected into the abdominal cavity twice a week for two weeks. The tumor size, mouse weight and mental state were recorded. Immunohistochemistry was used to detect the expression levels of Ki67 and PCNA, while the expression of Caspase-3 and Bax was analyzed using Western blotting.Results The duration of raltitrexed treatment was shorter and the body weight of the nude mice was lower than those of the control group. The tumor inhibition rate of the low-dose group and high-dose group was 27.54% and 44.20% respectively, so there was significant difference between the two groups. IHC Results showed that the Ki67 positive rate of cells was 58.95% and 42.16% respectively in the low-dose group and high-dose group, while the PCNA positive rate of cells was 51.36% and 37.27% respectively. Significant difference of Ki67 and PCNA expressions was found between these groups(P<0.05). Western blotting showed increased expressions of Caspase-3 and Bax in the two treatment groups(P<0.05), especially in the high-dose group (P<0.05).Conclusions Raltitrexed can inhibit human gastric cancer xenografts in nude mice.The mechanism may be related to enhanced expressions of Caspase-3 and Bax that promoted apoptosis.