Exploration of the Use of Epigenetic Therapy to Enhance the Effectiveness of Taxol Treatment

摘要

The RASSF1A tumor suppressor is frequently inactivated by aberrant promoter methylation leading to transcriptional silencing in ovarian cancer. Our preliminary data implicated loss of expression of RASSF1A in the acquisition of resistance to Taxol in ovarian cancer. We have now shown that experimental inactivation of RASSF1A does indeed induce resistance to Taxol mediated cell death, apoptosis and induction of tubulin polymerization. Furthermore, we have been able to reverse this effect by the use of a novel combination of drugs that inhibit DNA methylation to obtain a synergistic reactivation of RASSF1A expression. This provides proof of principal for the use of epigenetic therapy to overcome Taxol resistance in ovarian cancer.