Sodium butyrate inhibits the proliferation of temozolomide-resistant glioblastoma (A172) and lung adenocarcinoma (A549) cells and biphasically regulates EGFR expression

Sodium butyrate inhibits proliferation of TMZ-resistant A172 glioblastoma and A549 lung adenocarcinoma cells while biphasically regulating EGFR expression, with activity at 0.5–2.5 mM in resistant sublines.

• Why it matters: TMZ resistance leaves few options, and epigenetic MGMT silencing makes HDAC inhibition a rational partner; the key gap is whether sodium butyrate retains anti-tumor activity in resistant cells.
• What they did: In A172 and A549, NaB (class I/IIa HDAC inhibitor) was tested for concentration-dependent effects on proliferation and EGFR exon 2–5 mRNA/protein, alone and with TMZ (3 µM) in parental and stepwise TMZ-resistant sublines.
• The result: NaB reduced proliferation from 0.31 mM and induced EGFR exon 2–5 mRNA at 0.15 mM (A172) and 0.30 mM (A549) but suppressed it at higher doses; in resistant sublines, TMZ 10 µM alone had no effect, while NaB 0.5 and 2.5 mM inhibited proliferation, with combination-to-TMZ ratios not lower than parental lines (A172 0.70 vs 0.86; A549 0.49 vs 0.58).