Deoxyelenhantopin induces apoptosis via oxidative stress and enhances gemcitabine sensitivity in vitro and in vivo through targeting the NF-κB signaling pathway in pancreatic cancer

Pancreatic cancer is a highly invasive malignant tumor of the digestive system with an unfavorable prognosis worldwide. This trait is thought to be largely attributed to chemoresistance. Chemotherapy is the only hope for patients with advanced pancreatic cancer. Therefore, seeking new effective chemotherapy drugs has become an urgent need. The purpose of our study was to explore whether deoxyelephantopin (DET), a sesquiterpene lactone, has a potential antitumor effect in pancreatic cancer. Additionally, the antitumor effects of DET alone or in combination with gemcitabine (GEM) and the potential mechanism of this combination were revealed. In vitro experiments showed that DET suppressed the proliferation, invasion and metastasis of pancreatic cancer cells, induced cell apoptosis via oxidative stress, and enhanced GEM sensitivity by inhibiting the NF-kappa B signaling pathway. Beyond that, in vivo experiments showed that DET not only inhibited pancreatic tumor growth and metastasis but also amplified the antitumor capacity of GEM, which was related to the downregulation of NF-kappa B and its downstream gene products. In summary, it is possible that DET could be developed as a single agent or combined with conventional chemotherapy drugs to improve the treatment of pancreatic cancer.