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1.
Chinese Pharmaceutical Journal ; (24): 473-478, 2014.
Artigo em Chinês | WPRIM | ID: wpr-859797

RESUMO

OBJECTIVE: To investigate the anti-tumor activity of a novel cyclophosphamide derivate 4, 6-diphenyl cyclophosphamide (9b) on cultured SK-OV3 (human ovarian cancer cell line) and 143B (human osteosarcoma cell line) cells in vitro aid S180 (mouse sarcoma cell line) and B16 (murine melanoma cell line) solid tumors in vivo, and its possible anti-tumor mechanism. METHODS: The inhibitory effects of 9b on SK-OV3 and 143B cells proliferation were analyzed by MTT assay in vitro. The effect of 9b on cell cycle distribution and apoptosis were evaluated by flow cytometry. To evaluate the anti-tumor effect of 9b in vivo, mouse model bearing inoculated S180 and B16 tumor were established. RESULTS: MTT assay revealed that 9b obviously suppressed SK-OV3 and 143B cells growth and proliferation in a dose-dependent manner within the concentration ranging from 3.7 to 300 Limol·L-1 and in a time-dependent manner from 24 to 72 h. The IC50 value of 9b was (71.27±1.08) μmol·L-1 for SK-OV3 cells, and (98.50±0.82) μmol·L-1 for 143B cells respectively when incubation for 48 h. The results of flow cytometry indicated that after treated for 48 h with different concentration of 9b, the ratios of 143 B cells in the G0/G1 phase and SK-OV3 cells in the G0/G1 phase and G2/M phase were significantly increased compared with control group (P<0.05, P<0.01), the apoptosis rate had significantly increased (P<0.05, P<0.01). 9b (3, 10 and 30 mg·kg-1·d-1) could significantly reduce tumor weight in the S180 and B16 solid tumor mouse model in vivo. CONCLUSION: 9b showed significantly anti-tumor activity both in vivo and in vitro, of which the mechanism might be associated with the change of cell cycle distribution and induction of tumor cell apoptosis.

2.
Acta Pharmaceutica Sinica ; (12): 44-49, 2014.
Artigo em Chinês | WPRIM | ID: wpr-297973

RESUMO

This study is to investigate the anti-tumor activities of a novel cyclophosphamide derivate 4, 6-diphenyl cyclophosphamide (9b) in vivo and in vitro, and its possible mechanism of action. The inhibitory effects of 9b on human hepatoma cell line HepG2, human breast carcinoma cell line MCF-7 and human myeloid leukemia cell line K562 were measured by MTT assay in vitro. Cell cycle distribution and apoptotic rate were evaluated by flow cytometry. To evaluate the anti-tumor effect of 9b in vivo, mouse model bearing inoculated H22 tumor was established. The results indicated that 9b could inhibit the proliferation of HepG2, MCF-7 and K562 cells in a dose and time dependent manner. The ICo50 values of 9b were 32.34 micromol.L-1 to HepG2 cells, 87.07 micromol.L-1 to MCF-7 cells and 149.10 micromol.L-1 to K562 cells after incubation for 48 h. The results of flow cytometry indicated that after being treated for 48 h with different concentrations of 9b, the ratios of HepG2, MCF-7 cells at the Go/G1 phase and K562 cells at the G0/Gl phase and G2/M phase increased significantly compared with control group, and the apoptotic rate increased with the increase of the concentration of 9b. 9b could significantly reduce tumor weight of H22 solid tumor mouse model in vivo. To summarize, 9b showed significantly anti-tumor activity in vivo and in vitro, of which the mechanism might be associated with the change of cell cycle distribution and induction of tumor cell apoptosis.


Assuntos
Animais , Feminino , Humanos , Masculino , Camundongos , Antineoplásicos Alquilantes , Química , Farmacologia , Apoptose , Ciclo Celular , Linhagem Celular Tumoral , Proliferação de Células , Ciclofosfamida , Química , Farmacologia , Relação Dose-Resposta a Droga , Concentração Inibidora 50 , Neoplasias Hepáticas Experimentais , Patologia , Estrutura Molecular , Distribuição Aleatória , Carga Tumoral
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