Investigation of mechanisms of drug resistance in malignant brain tumor stem cells

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Forty malignant glioma specimens were subjected to tissue culture to establish new clones of brain tumor stem cells(BTSC) in our laboratory, of which 10 samples formed neurosphere and 4 are expected to established as BTSC expressing stem cell markers, such as nestin. X01S, an established BTSC clone, developed intracerebral tumors when inoculated, and was resistant to temozolomide(TMZ) as well as apoptosis-inducing targeted therapeutics in vitro, whereas TMZ elongated survival of mice bearing intracerebral X01S xenografts. MGMT gene promoter was methylated in three out of four BTSC cells including X01S, suggesting that multiple complex pathways might be involved in regulation of TMZ sensitivity in BTSCs.