Griseofulvin Radiosensitizes Non-Small Cell Lung Cancer Cells and Activates cGAS

Extra copies of centrosomes are frequently observed in cancer cells. To survive and proliferate, cancer cells have developed strategies to cluster extra-centrosomes to form bipolar mitotic spindles. The aim of this study was to investigate whether centrosome approved treatment) inhibits CC, and combined with radiotherapy, resulted in a significant increase in the number of NSCLC cells with multipolar spindles, and decreased cell viability and colony formation ability in vitro. In vivo, GF treatment was well tolerated by mice, and the combined therapy of GF and radiotherapy resulted in a significant tumor growth delay. Both GF and radiotherapy treat-ment also induced the generation of micronuclei (MN) in vitro and in vivo and activated cyclic GMP-AMP synthase (cGAS) in NSCLC cells. A significant increase in downstream cGAS-STING pathway activation was seen after combination treatment in A549 radio-resistant cells that was dependent on cGAS. In conclusion, GF increased radiotherapy efficacy in lung cancer preclinical models in vitro and in vivo. This effect may be associated with the generation of MN and the activation of cGAS. These data suggest that the combination therapy of CCi, radiotherapy, and immunotherapy could be a promising strategy to treat NSCLC.

Automated summary

Extra copies of centrosomes are frequently observed in cancer cells and cancer cells have developed strategies to cluster extra-centrosomes. This study investigated the effects of centrosome approved treatment (CCi) and radiotherapy on lung cancer cells, and found that the combination therapy significantly increased the number of NSCLC cells with multipolar spindles, decreased cell viability and colony formation ability in vitro, and delayed tumor growth in vivo. Furthermore, the combination therapy induced the generation of micronuclei and activated cGAS and cGAS-STING pathway in NSCLC cells. These findings suggest that the combination therapy of CCi, radiotherapy, and immunotherapy could be a promising strategy to treat NSCLC.