Discussion
Although gain-of-function of p53 variants remains to be characterized, our findings provide new insight into the synergistical cell death by regulating ferroptosis and p53.
Methods
The therapeutic effect of RSL3 plus low-concentration PTX combination therapy was investigated in HPSCC cells harboring mutant p53 (mtp53). Relative cell viability, ferroptosis-specific lipid peroxidation and relevant protein expression were evaluated.
Results
We demonstrated that neither PTX nor RSL3 in low concentration caused significant cell death; however, the combination therapy is shown to induce ferroptosis and significant cell death in mtp53 HPSCC. We discovered that low-concentration PTX enhanced the RSL3-induced ferroptosis by upregulating mtp53 expression. Furthermore, mtp53-mediated transcriptional regulation of SLC7A11 could be the key determinant.