Hydrogen sulfide promotes cell proliferation of oral cancer through activation of the COX2/AKT/ERK1/2 axis

Abstract

Hydrogen sulfide, the third gaseous transmitter, is one of the main causes of halitosis in the oral cavity. It is generally considered as playing a deleterious role in many oral diseases including oral cancer. However, the regulatory mechanisms involved in the effects of hydrogen sulfide on oral cancer growth remain largely unknown. In the present study, we investigated the underlying mechanisms through CCK-8 assay, EdU incorporation, real-time PCR, western blot and pathway blockade assays. Our results showed that hydrogen sulfide promoted oral cancer cell proliferation through activation of the COX2, AKT and ERK1/2 pathways in a dose-dependent manner. Blocking any of the three above pathways inhibited hydrogen sulfide-induced oral cancer cell proliferation. Meanwhile, blockade of COX2 by niflumic acid downregulated NaHS-induced p-ERK and p-AKT expression. Inactivation of the AKT pathway by GSK690693 significantly decreased NaHS‑induced p-ERK1/2 expression, and inhibition of the ERK1/2 pathway by U0126 markedly increased NaHS-induced p-AKT expression. Either the AKT or ERK1/2 inhibitor did not significantly alter the COX2 expression level. Our data revealed, for the first time, that hydrogen sulfide promotes oral cancer cell proliferation through activation of the COX2/AKT/ERK1/2 axis, suggesting new potential targets to eliminate the effect of hydrogen sulfide on the development of oral cancer.

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Exogenous H2S exerts biphasic effects on porcine mammary epithelial cells proliferation through PI3K/Akt‐mTOR signaling pathway

“…In line with our results, it has been demonstrated that PI3 K/Akt‐mTOR signaling pathway is involved in regulating the proliferation of various cells such as myeloma cells (Wu, Dai, & Wang, ), Clear Cell Renal Cell Carcinoma (Kornakiewicz et al, ), thyroid cancer cell (Meng, Dong, et al, ), and human leukemia HL‐60 cells (Wu et al, ). Inconsistently, it has been reported that ERK signaling pathway is involved in H 2 S‐mediated cell proliferation of various cells, such as oral cancer cell (Zhang et al, ), neural stem cells (Liu et al, ), and human colon cancer cell (Cai et al, ). The distinct signaling pathways underlying H 2 S‐mediated cell proliferation might be due to the different cell types and culture systems.…”

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