Porphyromonas gingivalis Inhibits Ferroptosis in Esophageal Squamous Cell Carcinoma via Upregulation of HIF-1α
10.3870/j.issn.1672-0741.23.01.009
- VernacularTitle:牙龈卟啉单胞菌通过上调HIF-1α抑制食管鳞癌细胞铁死亡
- Author:
Ran GUO
1
,
2
;
Linlin SHI
;
Yueyue CHENG
Author Information
1. 河南科技大学第一附属医院(临床医学院),肿瘤医院,河南省微生态与食管癌防治重点实验室,河南省肿瘤表观遗传重点实验室,洛阳 471003
2. 河南科技大学基础医学与法医学院,洛阳 471023
- Keywords:
Porphyromonas gingivalis;
esophageal squamous cell carcinoma;
ferroptosis;
HIF-1α
- From:
Acta Medicinae Universitatis Scientiae et Technologiae Huazhong
2023;52(6):749-755
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the mechanism underlying the suppressive effect of Porphyromonas gingivalis(P.gingivalis)on ferroptosis in esophageal squamous cell carcinoma(ESCC).Methods ESCC cells infected with P.gingivalis and uninfected control cells were treated with ferroptosis inducer RSL3 followed by measurements of cell viability,malondialde-hyde(MDA),reactive oxygen species(ROS),and the expression of glutathione peroxidase 4(GPX4).Moreover,the expression of hypoxia-inducible factor-1α(HIF-1α)and its target genes were detected by qPT-PCR,Western blotting or immunohistochem-istry in ESCC tissue and cells under the condition of P.gingivalis infection.The effect of P.gingivalis infection combined with the HIF-1α inhibitors LW6 and RSL3 on ferroptosis in ESCC was detected in vitro and in vivo.Results P.gingivalis infection of the ESCC cells resulted in an increase of the cell viability(P＜0.05),decreased levels of intracellular ROS(P＜0.05)and MDA(P＜0.05)and increased the expression of GPX4 compared with RSL3 treatment alone.In ESCC tissues,the increased a-bundance of P.gingivalis was correlated with upregulation of HIF-1α.Furthermore,P.gingivalis infection induced upregula-tion of HIF-1α and its target genes.LW6 promoted ferroptosis via inhibiting the HIF-1α upregulation induced by P.gingivalis infection in vitro and in vivo.Conclusion HIF-1α renders resistance to ferroptosis in P.gingivalis infected ESCC.Combination of HIF-1α inhibitory agents and ferroptosis inducing agents might be a novel therapeutic strategy in ESCC care.
