Abstract 4247: Iron controlled treatment can be novel therapeutic agent and biomarker of Bevacizumab

Abstract

Abstract [Introduction] Lung cancer is one of the most aggressive malignancies with poor prognosis. Many kinds of new medicine for chemotherapy have been developed and introduced in clinical practice, whereas the mortality has not been satisfied. Furthermore, development of new medicine for chemotherapy costs a vast sum of money, which leads expensive treatment. Therefore, It's expected that development of new strategy extremely enhances the efficacy of ordinary therapeutic strategy. Iron metabolism and its relationship with cancer cell have been studied for a long time. Iron overload is known to induce some kinds of cancer, which suggests that prevention of iron overload could be a therapeutic strategy of cancer prevention. In fact, iron deficiency is also known to suppress the tumor growth in vivo study. However the efficacy is not superior to the ordinary chemotherapy, it's not a standard therapeutic strategy of cancer. In this study, we demonstrated that iron deficiency induced the suppression of the tumor growth and unwillingly up-regulation of angiogenesis in vitro and in vivo studies. Moreover using Bevacizumab together strongly suppressed the tumor growth in NSCLC. This result suggests that Iron controlled treatment can be novel therapeutic agent and biomarker of Bevacizumab. [Materials and Methods] A549, H1299 NSCLC cell lines were used. In vivo study, Normal diet and Iron deficient diet are prepared. Normal diet and Iron deficient diet were fed for 3 weeks before implantation of A549 cells in athymic male nude mice(n=8/group). In Bevacizumab administration study, as shown above, Bevaicuzmab(5 mg/kg) was administrated twice a week in each diet group. In vitro study, Iron chelator deferasirox was used in vitro study. Cell viability was determined by WST-1 assay. Cell cycle analysis was measured by flow cytometry. To determine angiogenesis via hypoxia, western blotting analysis and VEGF ELISA assay were done. [Results] Tumor growth was suppressed in iron deficient diet group (p=0.0037). Bevacizumab revealed to have an additive effect to inhibit the tumor growth. Deferasirox reduces A549 and H1299 cell proliferation in a concentration manner via cell cycle arrest. Deferasirox induces VEGF in A549 and H1299 supernatant via up-regulation of HIF1a. [Conclusion] Iron controlled treatment can be novel therapeutic agent and biomarker of Bevacizumab. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4247. doi:10.1158/1538-7445.AM2011-4247