Glioblastoma is the most common malignant
brain tumor in adults and it is currently treated with a combination of
surgery, radiotherapy and chemotherapy with temozolomide (TMZ). Many patients
show resistance to TMZ, which is a challenge in the treatment of this type of
brain cancer.
New
strategies are being tested, like the inhibition of EZH2, a histone
methyltransferase which is overexpressed in cancer cells, leading to
angiogenesis and metastasis. In this work, the EZH2 inhibitor DZNeP was tested
in A172 glioblastoma cells and in A172-TMZ-resistant glioblastoma cells.
Inhibition of cell proliferation, adhesion,
colony formation, and migration was noted in control and TMZresistant
glioblastoma cells after DZNeP treatment. At the level of EZH2 target gene
expression, DZNeP decreased EZH2 expression, and increased the expression of
its target genes (E-cadherin and TIMP3), which might probably contribute to
inhibiting the development of a cancer metastatic phenotype.
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