Metformin treatment reduces temozolomide resistance of glioblastoma cells

• DOI: 10.18632/oncotarget.12859
• Publication Date: 2016-10-24T20:47:34Z
• Authors: Seung Ho Yang; Shenglan Li; Guangrong Lu; Haipeng Xue; Dong H. Kim; Jay-Jiguang Zhu; Ying Liu
• Keywords: Temozolomide; Neurosphere

It has been reported that metformin acts synergistically with temozolomide (TMZ) to inhibit proliferation of glioma cells including glioblastoma multiforme (GBM). However, the molecular mechanism underlying how exerts its anti-cancer effects remains elusive. We used a combined experimental and bioinformatics approach identify genes complex regulatory/signal transduction networks are involved in restoring TMZ sensitivity GBM after treatment. First, we established resistant cell lines found regained further identified down-regulates SOX2 expression TMZ-resistant cells, reduces neurosphere formation capacity inhibits xenograft growth vivo. Finally, global gene profiling data reveals multiple pathways treatment related changes, fatty acid metabolism RNA binding splicing pathways. Our work provided insight mechanisms on potential synergistic glioblastoma, which will turn yield potentially translational value for clinical applications.