Porphyromonas gingivalis Inhibits Ferroptosis via HIF-1α-mediated Mitophagy Enhancement in Esophageal Squamous Cell Carcinoma
10.3870/j.issn.1672-0741.24.12.026
- VernacularTitle:牙龈卟啉单胞菌通过HIF-1α增加线粒体自噬活性抑制食管鳞癌细胞铁死亡
- Author:
Yueyue CHENG
1
;
Ran GUO
;
Heqian ZHANG
Author Information
1. 河南科技大学临床医学院,河南科技大学第一附属医院,肿瘤医院,省部共建食管癌防治国家重点实验室,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
- Publication Type:Journal Article
- Keywords:
esophageal squamous cell carcinoma;
Porphyromonas gingivalis;
mitophagy;
HIF-1α;
ferroptosis
- From:
Acta Medicinae Universitatis Scientiae et Technologiae Huazhong
2025;54(4):470-476
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the molecular mechanism of ferroptosis inhibition induced by Porphyromonas gingi-v alis(Pg)in esophageal squamous cell carcinoma(ESCC).Methods Pg-infected KYSE30 cells and KYSE70 cells as well as un-infected control cells were insulted with RSL3,followed by measurement of mitophagy and mitochondrial reactive oxygen spe-cies(mitoROS)using fluorescent confocal microscopy.The ferroptosis-related markers including malondialdehyde(MDA)and glutathione peroxidase 4(GPX4)were gauged after mitochondrial autophagy inhibitor Mdivi-1 treatment in KYSE30 cells and KYSE70 cells.Hypoxia inducible factor-1α(HIF-1α)was activated or inhibited,respectively,followed by evaluation of mitophagy using confocal immunofluorescenct microscopy as well as the expression levels of SLC39A14 and IREB2 mRNA and protein u-sing Western blotting and RT-PCR.Results RSL3-induced ferroptosis in KYSE30 cells and KYSE70 ESCC cells was accompa-nied by the decrease in mitophagy activity.Pg infection alone increased mitophagy activity in ESCC cells,and combined treat-ment with Pg and RSL3 reversed the inhibitory effects on mitophagy and the subsequent occurrence of ferroptosis in ESCC cells induced by RSL3.Inhibition of mitophagy by Mdivi-1 rescued the anti-ferroptosis effect exerted by Pg infection.In ESCC cells,HIF-1α inhibition downregulated the mRNA and protein expression levels of SLC39A14 and IREB2 paralleled by mitophagy suppression,whereas HIF-1α activation reversed these effects.Conclusion Pg inhibits ferroptosis via HIF-1α-mediated mitoph-agy activation in ESCC.
