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

Zhang,Shuai; Bian,Huan; Li,Xiaoxu; Wu,Huanhuan; Bi,Qingwei; Yan,Yingbin; Wang,Yixiang

doi:10.3892/or.2016.4691

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

Authors:
- Shuai Zhang
- Huan Bian
- Xiaoxu Li
- Huanhuan Wu
- Qingwei Bi
- Yingbin Yan
- Yixiang Wang
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Affiliations: Central Laboratory, Peking University School and Hospital of Stomatology, Beijing, P.R. China, Department of Stomatology, The First Affiliated Hospital of the Chinese PLA General Hospital, Beijing, P.R. China, Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing, P.R. China, The Second Dental Center, Peking University School and Hospital of Stomatology, Beijing, P.R. China, Department of Oral Surgery, Hospital for Oral Disease Prevention and Treatment, Harbin, Heilongjiang, P.R. China, Department of Oral and Maxillofacial Surgery, Tianjin Stomatological Hospital, Tianjin, P.R. China
Published online on: March 17, 2016 https://doi.org/10.3892/or.2016.4691
Pages: 2825-2832

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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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