Hydrogen sulfide (H2S) participates in multifarious physiological and pathophysiologic progresses of
cancer both in vitro and in vivo. We have previously demonstrated that exogenous H2S promoted
liver cancer cells proliferation/anti‑apoptosis/angiogenesis/migration effects via amplifying the activation of NF-κB pathway. However, the effects of H2S on
cancer cell proliferation and apoptosis are controversial and remain unclear in C6 glioma cells. The present study investigated the effects of exogenous H2S on
cancer cells growth via activating p38 MAPK/ERK1/2-COX-2 pathways in C6 glioma cells. C6 glioma cells were treated with 400 µmol/l
NaHS (a donor of H2S) for 24 h. The expression levels of phosphorylated (p)-p38 MAPK, total (t)-p38 MAPK, p-ERK1/2, t-ERK1/2,
cyclooxygenase-2 (COX-2) and
caspase-3 were measured by western blotting assay. Cell viability was detected by Cell Counting Kit-8 (CCK-8). Apoptotic cells were observed by Hoechst 33258 staining assay. Cell proliferation was directly detected under fully automatic inverted microscope. Exposure of C6 glioma cells to
NaHS resulted in cell proliferation, as evidenced by an increase in cell viability. In addition,
NaHS treatment reduced apoptosis, as indicated by the decreased apoptotic percentage and the cleaved
caspase-3 expression. Importantly, exposure of the cells to
NaHS increased the expression levels of p-p38 MAPK, p-ERK1/2 and COX-2. Notably, co-treatment of C6 glioma cells with 400 µmol/l
NaHS and AOAA (an inhibitor of CBS) largely suppressed the above
NaHS-induced effects. Combined treatment with
NaHS and
SB203580 (an inhibitor of p38 MAPK) or
PD-98059 (an inhibitor of ERK1/2) resulted in the synergistic reduction of COX-2 expression and increase of
caspase-3 expression, a decreased number of apoptotic cells, along with decreased cell viability. Combined treatment with
NS-398 (an inhibitor of COX-2) and
NaHS also resulted in the synergistic increase of
caspase-3, a decreased in the number of apoptotic cells and the decrease in cell viability. The findings of the present study provide novel evidence that p38 MAPK/ERK1/2-COX-2 pathways are involved in
NaHS-induced
cancer cell proliferation and anti-apoptosis in C6 glioma cells.