1.Department of Medical Oncology, Chuzhou Clinical College of Anhui Medical University, Chuzhou First People’s Hospital, Chuzhou 239000,China; 2.Department of Medical Oncology, PLA Cancer Center, General Hospital of Eastern Theater Command, Nanjing 210002,China
Abstract：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.
薛松, 陈映霞, 秦叔逵, 蒋宗惠, 董祥宁. 雷替曲塞对人胃癌细胞MGC-803裸鼠移植瘤的抑制作用[J]. 武警医学, 2019, 30(7): 611-614.
GUO Shanshan, ZHANG Dan, YE Qi, LI Na, ZHU Chenghong, SONG Xupeng, TU Yue, PANG Xipeng. Inhibitory effect of raltitrexed on MGC-803 human gastric cancer xenografts in nude mice. Med. J. Chin. Peop. Armed Poli. Forc., 2019, 30(7): 611-614.
Xue S, Chen Y X, Qin S K, et al. Raltitrexed induces mitochondrialmediated apoptosis in sgc7901 human gastric cancer cells [J]. Mol Med Rep, 2014,10(4):1927-1934.
De M P R, Lima de D A, Pauli K B, et al. Molecular docking to Toxoplasma gondii thymidylate synthase-dihydrofolate reductase and efficacy of raltitrexed in infected mice.[J]. Parasitol Res, 2018, 117(14):1-7.
Tan P P, Zhou B H, Zhao W P, et al. Mitochondria-mediated pathway regulates C2C12 cell apoptosis induced by fluoride[J]. Biol Trace Elem Res, 2018(1):1-8.
Ashkenazi A, Fairbrother W J, Leverson J D, et al. From basic apoptosis discoveries to advanced selective BCL-2 family inhibitors.[J].Nat Rev Drug Discov, 2017, 16(4):273-284.
2019, Vol. 30 
