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[Effect of ACBP-S on cell cycle and apoptosis in human gastric cancer cells].
- Source :
-
Zhonghua zhong liu za zhi [Chinese journal of oncology] [Zhonghua Zhong Liu Za Zhi] 2008 Jun; Vol. 30 (6), pp. 422-7. - Publication Year :
- 2008
-
Abstract
- Objective: To explore the impact of anti-cancer bioactive peptide-S (ACBP-S) on cell proliferation, cell cycle and apoptosis in human stomach cancer cell line MGC-803 cells.<br />Methods: (1) The cultured MGC-803 cells were treated with ACBP-S at various concentrations for 24, 48, 72 h, respectively. The inhibition rate of proliferation of MGC-803 cells were evaluated by MTT assay. Cell apoptosis was observed by transmission electron microscopy. Cell cycle and apoptosis were analyzed by flow cytometry (FCM). RT-PCR was used to assay the changes of p27 mRNA expression. Immunocytochemistry was used to detect the changes of expression of p27, PCNA, Bax, Bcl-2 proteins, respectively. (2) a nude mouse xenograft model with gastric carcinoma cell was established. ACPB-S was administered into the tail vein of the mice in a dose of 7 microg, every other day, and the mice were killed after two weeks. The tumors were taken off for further analysis.<br />Results: (1) ACBP-S at concentrations of 5.0, 10.0 and 15.0 microg/ml inhibit the growth of MGC-803 cells in a concentration- and time-dependent manner. The concentration of ACBP-S at 20.0 microg/ml showed an inhibition rate of (86.6 + 0.1)%. Typical apoptotic changes were observed under the transmission electron microscope. The result of FCM in the range of 5.0 and 20.0 microg/ml for 24 h showed higher early apoptosis rates, (5.7 +/- 0.2)% and (13.9 +/- 0.6)%, respectively, with s significant difference compared with that of the control group (P < 0.05). The ratio of G0/G1 was significantly increased with the increase of incubation time at 20 microg/ml. RT-PCR showed that the expression of p27 mRNA in MGC-803 cells was markedly increased after ACBP-S treatment. (2) After ACBP-S administration the tumor growth in nude mice was inhibited by 34.2%. More apoptotic and necrotic cells were observed in the mice of treatment group by histological examination with HE staining. The immunocytochemistry demonstrated that the expression of Bax protein was significantly increased and Bcl-2 and PCNA protein expressions were significantly decreased after ACBP-S treatment.<br />Conclusion: ACBP-S has marked inhibiting effect upon the growth of MGC-803 cells inducing more apoptosis. The anti-cancer mechanism is probably related with its regulatory effects on cell cycle and apoptosis in the tumor cells.
- Subjects :
- Animals
Cell Line, Tumor
Cell Proliferation
Cyclin-Dependent Kinase Inhibitor p27
Dose-Response Relationship, Drug
Humans
Intracellular Signaling Peptides and Proteins genetics
Mice
Mice, Nude
Neoplasm Transplantation
Peptides administration & dosage
Proliferating Cell Nuclear Antigen metabolism
Proto-Oncogene Proteins c-bcl-2 metabolism
RNA, Messenger metabolism
Stomach Neoplasms metabolism
bcl-2-Associated X Protein metabolism
Apoptosis drug effects
Cell Cycle drug effects
Intracellular Signaling Peptides and Proteins metabolism
Peptides pharmacology
Stomach Neoplasms pathology
Subjects
Details
- Language :
- Chinese
- ISSN :
- 0253-3766
- Volume :
- 30
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Zhonghua zhong liu za zhi [Chinese journal of oncology]
- Publication Type :
- Academic Journal
- Accession number :
- 19024515