Project description:Doxorubicin (DOXO), a chemotherapeutic drug, is cardiotoxic. We hypothesized that folic acid is an effective therapeutic agent in a mouse model of DOXO-induced cardiotoxicity. We performed genome-wide expression profiling to identify the underlying mechanisms.
Project description:Doxorubicin (DOXO), a chemotherapeutic drug, is cardiotoxic. We hypothesized that folic acid is an effective therapeutic agent in a mouse model of DOXO-induced cardiotoxicity. We performed genome-wide expression profiling to identify the underlying mechanisms. Male C57Bl6 2-mo old mice received DOXO (1x20 mg/kg, ip) or saline (sham). FA (10 mg/d) or placebo (plac) was administered 7d before DOXO administration until the end of the experiment (10d).
Project description:The FDA approved drug Doxorubicin provokes copious irreversible cardiotoxicity and even increases the risk of heart failure. Considering the multiple and interacted molecular pathways in cancer, there is a big possibility that tumors are simultaneously sensitive to different drugs. This makes achievable to study the combinations of drug, having the virtues of less toxicity, higher efficacy and potentially antagonizing drug resistance in cancer therapy. In the present study, we addressed the synergistic effects of ginsenoside Rh2 on doxorubicin-treated breast cancer bearing mice. We showed that Rh2 significantly enhanced the antitumor effects of doxorubicin and greatly attenuated the cardiotoxicity. Transcriptomic changes can clearly distinguish the chemotherapeutic groups and non-treated control groups. Transcriptomic analysis domestrated that Rh2 protection involved in multiple vital pathways including cellular senescece, fibrosis remodeling, apoptosis and inflammation.
Project description:The FDA approved drug Doxorubicin provokes copious irreversible cardiotoxicity and even increases the risk of heart failure. Considering the multiple and interacted molecular pathways in cancer, there is a big possibility that tumors are simultaneously sensitive to different drugs. This makes achievable to study the combinations of drug, having the virtues of less toxicity, higher efficacy and potentially antagonizing drug resistance in cancer therapy. In the present study, we addressed the synergistic effects of ginsenoside Rh2 on doxorubicin-treated breast cancer bearing mice. We showed that Rh2 significantly enhanced the anti-cancer effects of doxorubicin and greatly attenuated the cardiotoxicity. Transcriptomic changes can clearly distinguish the chemotherapeutic groups and non-treated control groups. Transcriptomic analysis domestrated that Rh2 protection involved in multiple vital pathways including cellular stress, apoptosis and inflammation.
Project description:Anthracyclines such as doxorubicin (Dox) are effective chemotherapeutic agents, however their use is hampered by subsequent cardiotoxicity risk. Our understanding of cardiomyocyte protective pathways activated following anthracycline-induced cardiotoxicity (AIC) remains incomplete. Insulin-like growth factor binding protein (IGFBP) 3 (Igfbp-3), the most abundant IGFBP family member in the circulation, is associated with effects on the metabolism, proliferation, and survival of various cells. Whereas Igfbp-3 is induced by Dox in the heart, its role in AIC is ill-defined. We investigated molecular mechanisms as well as systems-level transcriptomic consequences of manipulating Igfbp-3 in AIC using neonatal rat ventricular myocytes and human induced pluripotent stem cell-derived cardiomyocytes.
Project description:Doxorubicin is a widely used anti-cancer drug, and its toxicological effects on healthy tissues, especially the heart, remains challenging in therapy. To explore the potential targets that ameliorate doxorubicin-induced cardiotoxicity (DIC), we aimed to investigate the role that macrophages play in the DIC development. Senescence of RAW264.7 cells was induced through doxorubicin administration in the experiment, and the transcription of secretory components was analyzed in this study.
