OncoTargets and Therapy (Aug 2020)
A New Fusion Peptide Targeting Pancreatic Cancer and Inhibiting Tumor Growth
Abstract
Lei Zheng,1 Bo Zhang,1,2 Xiaoman He,1 Guodong Cao,1 Yongzhou Li,1 Kailun Cai,1 Bin Yang,1,2 Yulian Wu1,2 1Department of Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310000, People’s Republic of China; 2Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Cancer Institute, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310000, People’s Republic of ChinaCorrespondence: Yulian Wu Email [email protected]: Pancreatic cancer is a highly malignant tumor of the digestive system. Early pancreatic cancer is often difficult to diagnosis due to its atypical clinical symptoms. Patients with pancreatic cancer have a very poor prognosis because they have lost the opportunity for radical surgical tumor resection and they are less sensitive to the clinically used radiotherapy and chemotherapy.Methods: In this study, a peptide targeting pancreatic cancer cells was screened by phage display technology, and its targeting property was evaluated in vitro using PANC1 cells by fluorescence imaging and flow cytometry. Furthermore, the targeting peptide was conjugated to the pro-apoptotic KLAKLAKKLAKLAK (KLA), the fusion peptide and its targeting ability that allowing KLA to specifically enter pancreatic tumor cells in vitro and in vivo was confirmed by fluorescence imaging and in vivo imaging system (IVIS). Its mechanism was determined using flow cytometry, mitochondrial membrane potential evaluation and Western blot. The inhibitory effect on pancreatic tumor growth and toxic effects were evaluated by animal experiment.Results: Due to the internalization facilitated by the targeting mechanism of the targeting peptide, KLA specifically entered pancreatic cancer cells, destroyed mitochondria and induced apoptosis. The fusion peptide and its targeting ability that allowing KLA to specifically enter pancreatic tumor cells and exert a significant inhibitory effect on pancreatic tumor growth with reduced toxic effects.Conclusion: This approach possesses potential advantages in the clinical diagnosis and treatment of pancreatic cancer.Keywords: targeting peptide, phage display technology, pancreatic cancer, KLA pro-apoptotic peptide, tumor growth inhibition
