NNK from tobacco smoking enhances pancreatic cancer cell stemness and chemoresistance by creating a β2AR-Akt feedback loop that activates autophagy.

ABSTRACT: Low responsiveness to chemotherapy is an important cause of poor prognosis in pancreatic cancer. Smoking is a high-risk factor for pancreatic cancer and cancer resistance to gemcitabine; however, the underlying mechanisms remain unclear. 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is the main metabolite of tobacco burning and has been shown to be associated with cancer development and chemoresistance. However, in pancreatic cancer, its mechanism remains poorly understood. In this study, we found that NNK promoted stemness and gemcitabine resistance in pancreatic cancer cell lines. Moreover, NNK increased autophagy and elevated the expression levels of the autophagy-related markers autophagy-related gene 5 (ATG5), autophagy-related gene 7 (ATG7), and Beclin1. Furthermore, the resul

SUBMITTER: Chen X 

PROVIDER: S-EPMC9348597 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature