ABSTRACT
Aim: To explore the effect of chloroxoquinoline (Chl) on cell proliferation, apoptosis and cell cycle in breast cancer cells and its potential mechanism. Methods: Breast cancer cells of Bcap37, MDA-MB-231 and MDA-MB-453 were treated with Chl at different doses. Cell proliferation was detected by MTT assay. Cell apoptosis and cell cycle were assayed by Annexin V-/PI kit using flow cytometry. Protein expression related to apoptosis and cell cycle were determined by Western blot. Results: Chl over the dose of 50 mg · L-1 inhibited cell proliferation in all three cell lines in a dose-dependent manner, and Ch; at the dose of 200 mg · L-1 exhibited similar efficiency as 40 mg · L-1 Paclitaxel did. When the cells were treated with 100 or 200 mg · L-1 Chl for 48 h, the apoptotic ratio was dose-dependently up-regulated in all three cell lines (P < 0.05), especially in the MDA-MB-231 cells. It was further proved by the protein expression of cleaved-PARP and cleaved-caspase related to apoptosis. On the contrary, Chl at the dose of 100mg · L-1 significantly increased the cell number of G2/M stage in Bcap37 and MDA-MB453 cells (P < 0. 05). Correspondingly, Western blot analysis demonstrated that Chl dose-dependently down-regulated p21 protein and up-regulated CDC2 protein, especially in Bcap37 and MDA-MB453 cells. Conclusions: Chl significantly inhibits cell proliferation in breast cancer cells of Bcap37, MDA-MB-231 and MDA-MB453, which may mainly result from its induction of cell apoptosis in MDA-MB-231 cells and cell cycle arrest in Bcap37 and MDA-MB-453 cells. These data provide new idea of chemotherapy using Chl for breast cancer treatment.
ABSTRACT
Objective To study whether Chloroxoquinoline could enhance the radiation sensitivity of Lewis lung cancer cells and xenograft tumors in tumor-bearing mice.Methods Both cell and animal experiments were divided into control group,drug group,irradiation group and combination group.MTT assay was used to detect the optical density of Lewis lung cancer cells cultured in vitro.The model of tumor-bearing mice was established first and then the tumor diameters of different groups were measured to figure out the tumor control rates and tumor growth delay.After irradiation,the blood samples in each group were collected to detect the amount of blood cells.Results MTT showed 24 hours after irradiation,the cell survival fraction of combination group was lower than that of irradiation group,but no statistical differences (P ＞ 0.05).However,48 hours later,the cell survival fraction of combination group was obviously lower than irradiation group with statistically significant differences( t = 3.22,4.23,4.46,4.58,P ＜ 0.05).Animal experiments showed the tumor growth curve of combination group was significantly lower than irradiation group.The tumor control rate and tumor growth delay of combination group was more above the other groups ( t = 3.15-3.59,P ＜ 0.05 ).Additionally,according to the analysis of blood samples,the hematological toxicity of chloroxoquinoline on mice was not found.Conclusion Chloroxoquinoline shows its radiation sensitizing effect on Lewis lung cancer cells and xenograft tumors in mice without hematological toxicity.