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TP 53 is associated with the resistance of cytotoxic treatment and patient prognosis, and the mutation rate of  TP 53 in esophageal squamous cell carcinoma ( ESCC ) is extraordinarily high, at over 90%.  PRIMA ‐1 (p53 re‐activation and induction of massive apoptosis) has recently been reported to restore the function of mutant  TP 53; however, its antitumor effect and mechanism in  ESCC  remain unclear. After evaluating the  TP 53 mutation status of a panel of 11  ESCC  cell lines by Sanger sequencing, we assessed the in vitro effect of  PRIMA ‐1 administration on cells with different TP53 status by conducting cell viability and apoptosis assays. The expression levels of proteins in  p 53‐related pathways were examined by Western blotting, while knockdown studies were conducted to investigate the mechanism underlying  PRIMA ‐1's function. An  ESCC  xenograft model was further used to evaluate the therapeutic effect of  PRIMA ‐1 in vivo.  PRIMA ‐1 markedly inhibited cell growth and induced apoptosis by upregulating Noxa expression in  ESCC  cell lines with  TP 53 missense mutations, whereas no apoptosis was induced in  ESCC  with wild‐type  TP 53 and  TP 53 with frameshift and nonsense mutations. Importantly, the knockdown of Noxa canceled the apoptosis induced by  PRIMA  treatment in  ESCC  cell lines with  TP 53 missense mutations.  PRIMA ‐1 administration, compared with placebo, showed a significant antitumor effect by inducing Noxa in the xenograft model of an  ESCC  cell line with a  TP 53 missense mutation.  PRIMA ‐1 exhibits a significant antitumor effect, inducing massive apoptosis through the upregulation of Noxa in  ESCC  with  TP 53 missense mutations.

PRIMA‐1 induces p53‐mediated apoptosis by upregulating Noxa in esophageal squamous cell carcinoma with TP53 missense mutation