Co-treatment with a C1B5 peptide of protein kinase Cγ and a low dose of gemcitabine strongly attenuated pancreatic cancer growth in mice through T cell activation
| Autor: | Masaaki Tamura, Alejandro Zulbaran-Rojas, Deepthi Uppalapati, Susumu Ishiguro, Naomi Ohta, Andreas G. Tzakos, Kelsey Monson, Charalampos G. Pappas, Atsushi Kawabata, Makoto Inui |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
T-Lymphocytes T cell Biophysics Peptide Deoxycytidine Biochemistry Article Mice 03 medical and health sciences Peritoneal cavity 0302 clinical medicine Cell Line Tumor Pancreatic cancer Antineoplastic Combined Chemotherapy Protocols medicine Animals Humans Molecular Biology Protein Kinase C Cell Proliferation chemistry.chemical_classification Dose-Response Relationship Drug Chemistry Cell Biology medicine.disease Gemcitabine Peptide Fragments Mice Inbred C57BL Pancreatic Neoplasms Granzyme B 030104 developmental biology medicine.anatomical_structure Cell culture Apoptosis 030220 oncology & carcinogenesis Cancer research Female medicine.drug |
| Zdroj: | Biochemical and Biophysical Research Communications. 495:962-968 |
| ISSN: | 0006-291X |
| Popis: | Although gemcitabine is an effective chemotherapeutic for pancreatic cancer, severe side effects often accompany its use. Since we have discovered that locally administered C1B domain peptides effectively control tumor growth without any side effects, the efficacy of co-treatment with this peptide and a low dose of gemcitabine on the growth of pancreatic cancer was examined. Two- and three-dimensional cell culture studies clarified that a co-treatment with C1B5 peptide and gemcitabine significantly attenuated growth of PAN02 mouse and PANC-1 human pancreatic cancer cells in 2D and 3D cultures. Although treatment with the low dose of gemcitabine alone (76%) or the C1B5 peptide alone (39%) inhibited tumor growth moderately, a co-treatment with C1B5 peptide and a low dose of gemcitabine markedly inhibited the growth of PAN02 autografts in the mouse peritoneal cavity (94% inhibition) without any noticeable adverse effect. The number of peritoneal cavity-infiltrating neutrophils and granzyme B+ lymphocytes was significantly higher in the co-treatment group than in the control group. A significant increase of granzyme B mRNA expression was also detected in human T cells by the co-treatment. Taken together, the current study suggests that C1B5 peptide offers a remarkably effective combination treatment strategy to reduce side effects associated with gemcitabine, without losing its tumoricidal effect. |
| Databáze: | OpenAIRE |
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