Elemene sensitizes pancreatic cancer cells to bortezomib by enhancing proteasome inhibition via molecular patch mechanism
Shurong Hou, Zhenzhen Li, Xiaoling Chen, Wenxin Wang, Ting Duan, Louis Scampavia, Yaxia Yuan, Timothy Spicer, Xiabin Chen, Tian Xie, Xiabin Chen, Tian Xie
Abstract
Pancreatic cancer* is one of the deadliest cancers, with an overall 5-year survival rate of less than 10% unchanged over the last 40 years. Approximately 80–85% of patients are diagnosed as advanced stage, which are not eligible for curative surgery. 1 Therapeutic options for advanced pancreatic cancer patients are still chemotherapy drugs with limited outcomes to improve patient survival and life quality. 2 New insights into developing safe and effective drugs for this lethal disease are urgently needed. Elemene (Ele) is a sesquiterpene natural product extracted from the Chinese herb Curcuma wenyujin . Developed with the guidance of “molecular compatibility theory”, 3 it is formulated as elemene liposome emulsion and approved by China’s Food and Drug Administration for treatment of some common cancers, including lung, liver, gastric, colorectal cancer and pancreatic cancer. 4 , 5 More interestingly, studies reported that elemene produces combinative effects with some chemotherapies, 6 , 7 such as oxaliplatin, gefitinib. Therefore, systematic exploration of the combined application of elemene with oncology drugs to achieve better therapeutic effects is of great clinical significance given the grim reality of pancreatic cancer treatment.