Inhibition of DNA Methyltransferase as a Novel Therapeutic Strategy to Overcome Acquired Resistance

• 作 者: 钱小军;李云天;余彦;杨芬;邓蓉;戢娇;焦琳;李轩;伍瑞燕;陈文丹;冯公侃;朱孝峰;
• 机 构: 中山大学肿瘤防治中心,华南肿瘤重点实验室,广东广州,510060
• 出 处: 2015医学前沿论坛暨第十四届全国肿瘤药理与化疗学术会议
• 发表日期: 2015年期

　　Purpose Dual PI3K/mTOR(phosphatidylinositol 3-kinase/mammalian target of rapamycin) inhibitors are being evaluated clinically for the treatment of tumors with a hyperactivated PI3K/mTOR pathway.However, unexpected outcomes were obtained in clinical studies of cancer patients with an aberrant PI3K pathway.In this study, we are going to exploring the mechanism(s) underlying these unexpected outcomes and finding combination therapies.Method We developed an acquired BEZ235-resistance cell lines(CNE2/235, HONE1/235).An Illumina Methylation BeasChip was performed in the sensitive parental cells and resistant cells to explore the whole gene methylation.RT-PCR,western blot assay was used to find the influence that PTEN hypermethylation on the PI3K/mTOR signaling pathyway and PPP2R2B hypermethylation on MYC and P70 phosphorylation to induce BEZ235 resistance.Western blot assay, MTT assay, nude mice tumor xenografts were used to find the effect of targeting methyltransferase.