Tumour radioresistance is a major problem for cancer radiation therapy. To identify the underlying mechanisms of this resistance, we used human non-small cell lung cancer (NSCLC) cell lines and focused on the Inhibitor of Apoptosis Protein (IAP) family, which contributes to tumourigenesis and chemoresistance. We investigated the possible correlation between radioresistance in six NSCLC cell lines and IAP protein levels and tested the radiosensitizing effect of birinapant in vitro, a molecule that mimics the second mitochondria-derived activator of caspase. We found that birinapant-induced apoptosis and inhibited the proliferation of NSCLC cells after exposure to radiation. These effects were induced by birinapant downregulation of cIAP protein levels and changes of cIAP gene expression. Overall, birinapant can inhibit tumour growth of NSCLC cell lines to ironizing radiation and act as a promising strategy to overcome radioresistance in NSCLC.
Keyphrases
- induced apoptosis
- small cell lung cancer
- endoplasmic reticulum stress
- advanced non small cell lung cancer
- signaling pathway
- oxidative stress
- gene expression
- radiation therapy
- brain metastases
- cell death
- cell cycle arrest
- endothelial cells
- amino acid
- epidermal growth factor receptor
- dna methylation
- dna damage response
- squamous cell carcinoma
- papillary thyroid
- induced pluripotent stem cells
- toll like receptor
- nuclear factor
- rectal cancer
- locally advanced