雷替曲塞对人胃癌裸鼠移植瘤生长的影响及其机制

摘要

Objective:This study was designed to explore the effects and mechanisms of raltitrexed on the growth of the human gastric cancer cell line (MGC-803) transplanted in nude mice. Methods: Models of MGC-803 xenograft transplanted in nude mice were established. Body weight, mental state, food, and stool of the nude mice were closely monitored, and the inhibitory action in the tu-mors was evaluated after drug intervention. Distribution and apoptosis of the tumor cells were examined through flow cytometric assay. P53 mRNA and protein expression levels were determined through reverse transcription-polymerase chain reaction and Western blot analysis. Changes among the three groups were compared. Results:Body weights and tumor volumes of the nude mice were lower in the raltitrexed and 5-fluorouracil (5-Fu) groups than those in the control group. Tumor inhibition ratios were 49.02%and 45.75%in the raltitrexed and 5-Fu groups, respectively. In the G0/G1 stage, the number of cells decreased in the raltitrexed and 5-Fu groups. Signifi-cant differences were found between the experimental and control groups (P<0.01). In the S stage, the number of cells increased in the raltitrexed and 5-Fu groups, with significant differences from the control group (P<0.01). P53 mRNA and protein expression levels in the raltitrexed and 5-Fu groups were significantly higher than those in the control group (P<0.01), but no significant differences were found between the raltitrexed and 5-Fu groups (P>0.05). Conclusion:Raltitrexed can inhibit the growth of MGC-803 xenograft trans-planted in nude mice and shows inhibitory effect similar to that of 5-Fu. Raltitrexed can induce the S-phase block of the cell cycle and cell apoptosis in the MGC-803 xenografts in the nude mice. This drug may exhibit an antitumor effect by upregulating the p53 mRNA and protein expression levels.%目的：初步探索雷替曲塞对人胃癌裸鼠皮下移植瘤生长的影响及其机制。方法：1）建立人胃癌细胞MGC-803裸鼠皮下移植瘤模型；2）药物干预后观察荷瘤鼠一般情况、体重、瘤重并计算抑瘤率；3）流式细胞仪测定瘤细胞的周期分布和凋亡；4）采用RT-PCR、Western blot印迹法检测各组肿瘤p53 mRNA及p53蛋白的表达水平。结果：经雷替曲塞及5-Fu作用后，与对照组相比，两组裸鼠的体重明显下降，瘤体积缩小，抑瘤率分别达到49.02%和45.75%。雷替曲塞组和5-Fu组瘤细胞的G0/G1期比例较对照组比例明显降低（P<0.01），而S期比例较对照组明显升高（P<0.01）。雷替曲塞组和5-Fu组裸鼠肿瘤p53 mRNA与蛋白表达水平均显著升高（P<0.01），但雷替曲塞组和5-Fu组之间并无差异。结论：1）雷替曲塞对人胃癌细胞MGC-803裸鼠移植瘤生长有抑制作用，且与5-Fu抑瘤效果相似；2）雷替曲塞可以诱导人胃癌细胞MGC-803裸鼠移植瘤细胞周期S期的阻滞，并诱导移植瘤细胞凋亡；3）雷替曲塞可通过上调p53 mRNA和蛋白的表达水平来发挥抑瘤作用。