Small-cell lung cancer (SCLC) is the most invasive of all lung cancer subtypes, and is characterized by its rapid response to chemotherapy resistance. Overcoming chemotherapy resistance is therefore the key to treating SCLC. P53 is mutated in most SCLCs, which has an effect of enhancing chemotherapy resistance. Regulation of p53 proteins by a variety of post-translational modifications, such as acetylation, which affects their function. Acetylation and deacetylation of p53 may be potential targets for modulating chemosensitivity. Recent studies have shown that SIRT3 acts as a deacetylase that regulates acetylation of p53. However, whether SIRT3 can regulate the post-translational modification of mutant p53 has not been studied. In the present study, we found that SIRT3 can deacetylate mutant p53, thus reducing its expression, inducing apoptosis in SCLC cells, and increasing SCLC chemosensitivity. The relationship between SIRT3 and mutant p53 could be the basis of a new SCLC treatment approach.
Keywords: Apoptosis; Deacetylation; Mutant p53; Sirtuin-3; Small-cell lung cancer.
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