The anti-fibrotic effect of GV1001 combined with gemcitabine on treatment of pancreatic ductal adenocarcinoma
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Joo Kyung Park1,*, Yejin Kim2,*, Hyemin Kim2,3, Jane Jeon2, Tae Wan Kim4, Ji-Hong Park5, Young-il Hwnag2, Wang Jae Lee2, Jae Seung Kang2,3
1Division of Gastroenterology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
2Laboratory of Vitamin C and Anti-Oxidant Immunology, Department of Anatomy and Cell Biology, Seoul National University College of Medicine, Seoul, Korea
3Institute of Allergy and Clinical Immunology, Seoul National University Medical Research Center, Seoul, Korea
4Department of Ophthalmology, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul, Korea
5Department of Rehabilitation Medicine, Seoul National University Bundang Hospital, Bundang-gu, Seongnam-si, Gyeonggi-do, Korea
*These authors have contributed equally to this work as first authors
Jae Seung Kang, email: [email protected]
Keywords: GV 1001, gemcitabine, xenograft tumor model, pancreatic ductal adenocarcinoma
Received: January 24, 2016 Accepted: August 23, 2016 Published: September 16, 2016
GV1001 is a telomerase-based cancer vaccine made of a 16-mer telomerase reverse transcriptase (TERT) peptide, and human TERT, the rate-limiting subunit of the telomerase complex, is an attractive target for cancer vaccination. The aim of this study was to evaluate the effect of telomerase peptide vaccination, GV1001 combined with gemcitabine in treatment of pancreatic ductal adenocarcinoma (PDAC). Human PDAC cell lines were used in vitro experiment and also, PDAC xenograft mice model was established using PANC1, AsPC1 and CD133+ AsPC1 (PDAC stem cell). Treatment groups were divided as follows; control, gemcitabine, GV1001, gemcitabine and GV1001 combination. The inflammatory cytokines were measured from the blood, and xenograft tumor specimens were evaluated. GV1001 treatment alone did not affect the proliferation or the apoptosis of PDAC cells. Gemcitabine alone and gemcitabine with GV1001 groups had significantly reduced in tumor size and showed abundant apoptosis compared to other treatment groups. Surprisingly, xenograft PDAC tumor specimens of gemcitabine alone group had been replaced by severe fibrosis whereas gemcitabine with GV1001 group had significantly less fibrosis. Blood levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-1β increased in gemcitabine alone group, however, it was decreased in gemcitabine with GV1001 group. GV1001 combined with gemcitabine treatment showed significant loss of fibrosis in tumor tissue as well as tumor cell death. Therefore, further investigation of GV1001 effect combined with gemcitabine treatment may give us useful insights to overcome the hurdle in anti-cancer drug delivery over massive fibrosis around PDACs.
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