Cuproptosis For Hpv+ Oral Squamous Cell Carcinoma

The number of oral squamous cell carcinoma (OSCC) caused by human papillomavirus (HPV) is increasing yearly. Cuproptosis is a type of death dependent on mitochondrial respiration. Previous studies have shown that HPV+ OSCC exhibit high levels of oxidative stress and enhanced cellular sensitivity to cuproposis, which may be related to HPV E6 and E7 proteins. Therefore, cuproptosis is expected to open up a new clinical treatment strategy for HPV+OSCC. The mitochondrial function status and oxidative stress level of cell lines were detected after knockdown of HPV+ OSCC E6/E7 genes and overexpression of E6/ E7 in HPV-OSCC. HPV+ and HPV-OSCC cells were treated with elesclomol and copper, and cell viability, oxidative stress levels and copper death markers were measured. A cell model of high/low oxidative stress was constructed to detect the correlation between the sensitivity of cuproptosis and oxidative stress. HPV+ humanized tumor mice were constructed to evaluate the therapeutic effect of elesclomol administration in vivo. Bio-informatics analysis revealed that the level of mitochondrial oxidative stress was higher in HPV+OSCC. ROS staining showed a decrease in reactive oxygen species levels after knockdown of E6/E7. The cell viability HPV+ OSCC was significantly inhibited after treated with 1 nmol/L elesclomol and 1 nmol/L copper. Cuproptosis has the potential to treat HPV+ OSCC.