Characterization and use of HapT1-derived homologous tumors as a preclinical model to evaluate therapeutic efficacy of drugs against pancreatic tumor desmoplasia

摘要: // Sujit Suklabaidya 1, 2 , Biswajit Das Syed Azmal Ali 3 Sumeet Jain Sharada Swaminathan 4 Ashok K. Mohanty Susen Panda 5 Pujarini Dash 1 Subhankar Chakraborty 6 Surinder Batra 7 Shantibhusan Senapati Tumor Microenvironment and Animal Models Laboratory, Department of Translational Research, Institute Life Sciences, Bhubaneswar, Odisha, India Manipal University, Manipal, Karnataka, Proteomics Structural Biology Biotechnology Department, National Diary Research Institute, Haryana, Bioengineering, School Chemical Biotechnology, SASTRA Thanjavur, Tamil Nadu, Veterinary Pathology, Odisha University Agriculture Technology, Mayo Clinic, Division Gastroenterology Hepatology, Rochester, MN, USA Biochemistry Molecular Biology, Buffett Cancer Center, Eppley for Nebraska Medical Omaha, NE, Correspondence to: Senapati, email: drsantibhusan@yahoo.com senapati@ils.res.in Keywords: pancreatic cancer, desmoplasia, HapT1, stellate cells, hamster homologous orthotopic model Received: March 04, 2016      Accepted: May 17, Published: 31, 2016 ABSTRACT Desmoplasia in human cancer (PC) promotes progression hinders effective drug delivery. The objectives this study were to characterize a PC Syrian golden investigate the effect anti-fibrotic (pirfenidone), antioxidant (N-acetyl cysteine, NAC) anti-addiction (disulfiram, DSF) drugs on desmoplasia tumor growth model. HapT1 cells when implanted orthotopically into hamsters formed tumors with morphological, cellular molecular similarities PC. Protein profiling activated (ha-PSCs) revealed expression proteins involved fibrosis, metastasis. Pirfenidone, suppressed desmoplastic response vivo ; these effects enhanced by co-administration NAC. Disulfiram alone or combination copper (Cu) was toxic PSCs vitro but DSF Cu accelerated . Moreover, had no tumor-associated desmoplasia. Overall, identifies HapT1-derived as useful tumor-directed therapeutics Pirfenidone NAC could be novel therapy warrants investigation subjects.