| Objective: To investigate the effects of 5-allyl-7-gen-difluoromethyllenechrysin (ADFMChR) on the viability and growth inhibition of cultured human lung cancer cell (A549) and Chinese hamster lung epithelial cell (CHL) in vitro, and to evaluate the therapeutic effect of ADFMChR on growth of human lung carcinoma xenografts in nude mouse model.Methods: Human lung carcinoma cells (A549) and Chinese hamster lung epithelial cells (CHL) were cultured in vitro. and the viability were examined by MTT assay. The trypan blue exclusion method was used to count the number of living and dead cells of A549 and CHL cells, then the survival rate and growth curve were achieved. Human lung carcinoma (A549) xenograft in nude mouse model was established to investigate the volume and weight of xenografts, the body weight without xenografts. HE staining was utilized to observe the histomorphology change of the xenografts. The expression of PCNA, VEGF and CD31 in xenografts were determined by immunohistochemistry.Results: The MTT assay showed that the proliferation inhibitory rates of A549 cell were 24.39%,47.66%,62.75%,73.35%,85.94% respectively after treatment with 1.0,2.0,4.0,8.0,16.0μM of ADFMChR for 48h. ADFMChR significantly suppressed proliferation of A549 cells in a concentration dependent manner, and its IC50 was 2.63μM. The efficacy of inhibition with ADFMChR was stronger than that of Chrysin (IC50 was 17.48μM ) and was similar to DDP (IC50 was 2.71μM). For CHL cell, the proliferation inhibitory rates were 3.95%,7.44%,13.89%,21.60%,27.43% respectively after CHL cell was treated with 1.0,2.0,4.0,8.0,16.0μM of ADFMChR for 48h. The IC50 was 44.89μM. The cytotoxicity of ADFMChR to CHL cells was lower than that of DDP (IC50 was 5.50μM) and was similar to Chrysin (IC50 was 45.03μM ). The selective index of ADFMChR (42. 96) was higher than those of ChR (2.58) and DDP (2.03).The living cell number were determined by the trypan blue exclusion method. The data showed that the growth inhibitory rates were 16.01%,39.07%,73.36% respectively after A549 cell was treated with 1.0,4.0,16.0μM of ADFMChR for 48h. ADFMChR significantly suppressed the growth of A549 cells in a concentration and time dependent manner, and its IC50 was 5.83μM. The efficacy of inhibition with ADFMChR was stronger than that of Chrysin (IC50 was 18.93μM ) and was similar to 5-FU (IC50 was 6.22μM). The results also showed that the growth inhibitory rates of CHL cell were 11.74%,22.65%,32.62% respectively after treatment with 1.0,4.0,16.0μM of ADFMChR for 48h. The IC50 was 68.52μM. The cytotoxicity of ADFMChR to CHL cells was lower than that of 5-FU (IC50 was 16.50μM) and was similar to Chrysin (IC50 was 99.22μM). The selective index of ADFMChR (11.75) was higher than those of ChR (5.24) and 5-FU (2.65).Administration of ADFMChR in nude mouse model indicated that it significantly inhibit the growth of human lung carcinoma xenografts in BALB/ c-nu mice. The tumor weight inhibitory rates of ADFMChR at 5.0,10.0,20.0 mg/kg were 42.98%,82.31% and 89.91% respectively.The immunohistochemistry staining showed that ADFMChR inhibited the expression of PCNA, VEGF and CD31 in human lung carcinoma xenografts cells in BALB/c-nu mice.Conclusion:1) ADFMChR had stronger cell proliferation and growth inhibition effect to human lung cancer cell (A549) than to Chinese hamster lung epithelial cell(CHL) and it possess the relative selectivity for cell proliferation and growth inhibition on A549 cell.2) ADFMChR significantly inhibited the growth of human lung carcinoma xenografts in BALB/ c-nu mice, in a dose dependent manner. 3) ADFMChR'S growth inhibition effect on human lung carcinoma xenografts may be associated with its down-regulation of PCNA, VEGF and CD31 expression of human lung carcinoma xenografts cells in BALB/ c-nu mice. .
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