Conclusions
Our results underscore that DEX reduces chemotherapy sensitivity by blunting therapy induced cellular senescence after chemotherapy in NSCLC, which may, at least in part, in a p53-dependent manner. These data therefore raise concerns about the widespread combined use of gluocorticoids (GCs) with antineoplastic drugs in the clinical management of cancer patients.
Methods
We examined in different human NSCLC cell lines and detected cellular senescence after cisplatin (DDP) treatment in the presence or absence of DEX. The in vivo effect of the combination of DEX and DDP was assessed by tumor growth experiments using human lung cancer cell lines growing as xenograft tumors in nude mice.
Results
Co-treatment with DEX during chemotherapy in NSCLC resulted in increased tumor cell viability and inhibition of TIS compared with DDP treated group. DEX co-treatment cells exhibited the decrease of DNA damage signaling pathway proteins, the lower expression of p53 and p21(CIP1), the lower cellular secretory program and down-regulation of NF-κB and its signaling cascade. DEX also significantly reduced DDP sensitivity in vivo. Conclusions: Our results underscore that DEX reduces chemotherapy sensitivity by blunting therapy induced cellular senescence after chemotherapy in NSCLC, which may, at least in part, in a p53-dependent manner. These data therefore raise concerns about the widespread combined use of gluocorticoids (GCs) with antineoplastic drugs in the clinical management of cancer patients.