The Study Of The Growth Suppression Induced By Ibandronate Combined With Chemotherapeutics To Human Breast Carcinoma In Vitro

[Objective] To investigate the effect and mechanism of Ibandronate on drug sensitivity of Taxotere, Adriamycin and Gemcitabine in combined treatment, and then offer evidence for clinical application.[Methods] The inhibited rates of human breast carcinoma cells (MDA-MB453) treated by single Ibandronate, single chemotherapy, and combined treatment of Ibandronate and chemotherapy in different sequences were determined with MTT colorimetric assay. The changes in cell cycle of cells and apoptosis of every group were analysed by flow cytometry (FCM).[Results]1.Chemotherapeutic agents(IBN, TXT, ADM, GEM) could suppress proliferation or kill MDA-MB453 cells in vitro.2. The MTT colorimetric assay shows:(1) the groups that simultaneous treatment of TXT and IBN or IBN was used 24h later than TXT achieved maximum inhibition rate (P<0.01) and the interaction was synergistic;and the groups of IBN first used also got better inhibition rate(P<0.05) than monotherapy, displaying additive action; (2) All the groups that using ADM combined IBN achieved better inhibiton rate(P<0.05) than the monotherapy group of ADM, and showed synergistic interaction or additive action.; especially the group that using IBN 12h after ADM got the maximum inhibition rate;(3) The combinations of IBN and DDP achieved better inhibition than the monotherapy of GEM (P＜0.05), and showed additive interaction or synergistic interaction; and the group that IBN was used 24h before GEM showed the best inhibition rate.3,Flow cytometry showed that:(1) IBN could induce S phase arrest; (2) Chemotherapeutic drug (TXT) alone blocked the cell cycle in the G2/M compartment of cell cycle. Compared with the group of chemotherapy alone, the proportions of S and G2/M phase cells in the group of simultaneous treatment of TXT and IBN increased obviously, while the proportions of G0/G1 phase cells decreased; and apoptotic rate was also maximum. But in the group of TXT used 24h before IBN,there is only S phase increased; (3) Single chemotherapeutic drug(ADM) arrested cell cycle progression in G2/M phase. Compared with the group of single chemotherapy, the group using IBN 12h after ADM resulted in the decrease of proportions of G0/G1 phase and the increase of S% G2/M phase, and also the apoptotic rate was the highest; and the groups using IBN fisrt showed G0/G1 increased;(4)Single chemotherapeutic drug(GEM) arrested cell cycle progression in S phase,and G0/G1 phase decreased. Compared with the group of single chemotherapy, the groups that using GEM 24h later than IBN resulted in the increase of proportions of S phase obviously, and the apoptotic rate of this group was the best; With the change of the sequence of the IBN-GEM application, the proportions of S phase decreased gradually.[Conclusion] Effects of combinations of Ibandronate and chemotherapeutic agents in different sequences is different:Combined with TXT, to use IBN later or simultaneous treatment of TXT and IBN might get the best inhibiton; Combined with ADM, using IBN 12h later than ADM could get the maximum inhibition rate; And combined with GEM, using GEM 24h later than IBN was the best choice. And Its mechanism may be related to the cell cycle changed and apoptosis induced.