Wang Hai-Jun, Liu Yu, Zhou Bao-Jun, Zhang Zhan-Xue, Li Ai-Ying, An Ran, Yue Bin, Fan Li-Qiao, Li Yong
1 Department of Surgery, Second Affiliated Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China.
2 Department of Biochemistry and Molecular Biology, Traditional Chinese Medical College, Hebei Medical University, Hebei Key Laboratory of Chinese Medicine Research on Cardio-Cerebrovascular Disease, Shijiazhuang, Hebei Province, China.
J Int Med Res. 2018 May;46(5):1756-1766. doi: 10.1177/0300060518761505. Epub 2018 Mar 23.
Objective To investigate the potential antitumour effects of [2-(6-amino-purine-9-yl)-1-hydroxy-phosphine acyl ethyl] phosphonic acid (CP) against gastric adenocarcinoma. Methods Human BGC-823 xenotransplants were established in nude mice. Animals were randomly divided into control and CP groups, which were administered NaHCO vehicle alone or CP dissolved in NaHCO (200 µg/kg body weight) daily, respectively. Tumour volume was measured weekly for 6 weeks. Resected tumours were assayed for proliferative activity with anti-Ki-67 or anti-proliferating cell nuclear antigen (PCNA) antibodies. Cell apoptosis was examined using terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) assays and with caspase-3 immunostaining. Proteins were measured by Western blotting. Results There was a significant reduction in tumour volume and a reduced percentage of Ki-67-positive or PCNA-positive cells in the CP group compared with the control group. The percentage of TUNEL-positive or caspase 3-positive cells significantly increased following CP treatment compared with the control group. Tumours from the CP group had higher levels of phosphorylated-extracellular signal-regulated kinase (p-ERK) and phosphorylated-AKT (p-AKT) compared with control tumours. Conclusion CP treatment inhibited tumour growth and induced tumour cell apoptosis in a nude mouse model of BGC-823 gastric adenocarcinoma. Activation of the AKT and ERK signalling pathways may mediate this antitumour activity.
目的 探讨[2-(6-氨基嘌呤-9-基)-1-羟基膦酰基乙基]膦酸（CP）对胃腺癌的潜在抗肿瘤作用。方法 在裸鼠体内建立人BGC-823异种移植瘤模型。动物随机分为对照组和CP组，分别每日给予单独的NaHCO载体或溶于NaHCO的CP（200 µg/kg体重）。每周测量肿瘤体积，持续6周。用抗Ki-67或抗增殖细胞核抗原（PCNA）抗体检测切除肿瘤的增殖活性。使用末端脱氧核苷酸转移酶介导的dUTP缺口末端标记（TUNEL）测定法和caspase-3免疫染色检测细胞凋亡。通过蛋白质印迹法测量蛋白质。结果 与对照组相比，CP组肿瘤体积显著减小，Ki-67阳性或PCNA阳性细胞百分比降低。与对照组相比，CP处理后TUNEL阳性或caspase 3阳性细胞百分比显著增加。与对照肿瘤相比，CP组肿瘤中磷酸化细胞外信号调节激酶（p-ERK）和磷酸化AKT（p-AKT）水平更高。结论 在BGC-823胃腺癌裸鼠模型中，CP治疗抑制肿瘤生长并诱导肿瘤细胞凋亡。AKT和ERK信号通路的激活可能介导这种抗肿瘤活性。
