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Inhibitory effects of CP on the growth of human gastric adenocarcinoma BGC-823 tumours in nude mice.
- Source :
-
The Journal of international medical research [J Int Med Res] 2018 May; Vol. 46 (5), pp. 1756-1766. Date of Electronic Publication: 2018 Mar 23. - Publication Year :
- 2018
-
Abstract
- 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 <subscript>3</subscript> vehicle alone or CP dissolved in NaHCO <subscript>3</subscript> (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.
- Subjects :
- Adenocarcinoma metabolism
Animals
Apoptosis drug effects
Cell Line, Tumor
Cell Proliferation drug effects
Diphosphonates administration & dosage
Female
Humans
Ki-67 Antigen metabolism
Mice, Inbred BALB C
Mice, Nude
Phosphatidylinositol 3-Kinases metabolism
Proliferating Cell Nuclear Antigen metabolism
Proto-Oncogene Proteins c-akt metabolism
Stomach Neoplasms metabolism
Adenocarcinoma pathology
Diphosphonates pharmacology
Stomach Neoplasms pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1473-2300
- Volume :
- 46
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- The Journal of international medical research
- Publication Type :
- Academic Journal
- Accession number :
- 29569987
- Full Text :
- https://doi.org/10.1177/0300060518761505