MACF1 knockdown in glioblastoma multiforme cells increases temozolomide-induced cytotoxicity / 南方医科大学学报

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the role of microtubule-actin crosslinking factor 1 (MACF1) in the response of glioma cells to temozolomide (TMZ).</p><p><b>METHODS</b>TMZ was applied to a human gliomablastoma cell line (U87) and changes in the protein expression and cellular localization were determined with Western blot, RT-PCR, and immunofluorescence. The responses of the cells with MACF1 expression knockdown by RNA interference to TMZ were assessed. TMZ-induced effects on MACF1 expression were also assessed by immunohistochemistry in a nude mouse model bearing human glioblastoma xenografts.</p><p><b>RESULTS</b>TMZ resulted in significantly increased MACF1 expression (by about 2 folds) and changes in its localization in the gliomablastoma cells both in vitro and in vivo (P<0.01). Knockdown of MACF1 reduced the proliferation (by 45%) of human glioma cell lines treated with TMZ (P<0.01). TMZ-induced changes in MACF1 expression was accompanied by cytoskeletal rearrangement.</p><p><b>CONCLUSION</b>MACF1 may be a potential therapeutic target for glioblastoma.</p>