Therapeutic potential of valsartan in overcoming chemoresistance in human glioblastoma

ObjectiveGlioblastoma multiforme (GBM) is the most frequently occurring central nervous system tumor in adults. GBM patients exhibit poor survival outcomes following standard treatment, with drug resistance playing a critical role in disease progression. This study aimed to evaluate the effects of valsartan, a renin-angiotensin system inhibitor, on GBM cell lines with and without temozolomide (TMZ) resistance.MethodsTMZ-resistant GBM clones were established by repeatedly exposing LN229 and GBM8401 human glioma cells to high doses of TMZ, followed by selective culture of the surviving populations. Tumorigenic potential was assessed using viability, sphere formation, invasion, and apoptosis assays. Gene expression was examined by sequencing and validated by quantitative polymerase chain reaction.ResultsValsartan reduced the proportion of viable GBM cells regardless of TMZ sensitivity. Flow cytometry and western blotting revealed increased apoptosis in GBM following valsartan treatment. RNA sequencing revealed that valsartan regulates the cell cycle and induces G1-phase arrest, as evidenced by cell cycle flow cytometry. Moreover, APLN, an angiogenesis-related gene, was identified as a potential downstream target whose expression is significantly inhibited by valsartan.ConclusionsThis study revealed that valsartan is a novel strategy for treating gliomas with drug resistance.