학술논문
Autophagy Inhibition Increased Sensitivity of Pancreatic Cancer Cells to Carbon Ion Radiotherapy.
Document Type
Academic Journal
Author
Sudo M; Department of Gastroenterological Surgery, Hyogo Medical University, Hyogo, Japan.; Tsutsui H; Department of Gastroenterological Surgery, Hyogo Medical University, Hyogo, Japan.; Hayashi S; Department of Microbiology, Hyogo Medical University, Hyogo, Japan.; Yasuda K; Department of Immunology, Hyogo Medical University, Hyogo, Japan.; Mitani K; Department of Gastroenterological Surgery, Hyogo Medical University, Hyogo, Japan.; Iwami N; Department of Physiology, Hyogo Medical University, Hyogo, Japan.; Anzai M; Osaka Heavy Ion Therapy Center, Osaka, Japan.; Tsubouchi T; Osaka Heavy Ion Therapy Center, Osaka, Japan.; Ishida M; Department of Pathology, Osaka Medical and Pharmaceutical University, Osaka, Japan.; Satoi S; Department of Surgery, Kansai Medical University, Osaka, Japan.; Division of Surgical Oncology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.; Kanai T; Osaka Heavy Ion Therapy Center, Osaka, Japan.; Hirono S; Department of Gastroenterological Surgery, Hyogo Medical University, Hyogo, Japan.; Hatano E; Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.; Fujimoto J; Department of Gastroenterological Surgery, Hyogo Medical University, Hyogo, Japan, sfujimo@hyo-med.ac.jp.; Osaka Heavy Ion Therapy Center, Osaka, Japan.
Source
Publisher: Cell Physiol Biochem Press GmbH & Co KG Country of Publication: Germany NLM ID: 9113221 Publication Model: Print Cited Medium: Internet ISSN: 1421-9778 (Electronic) Linking ISSN: 10158987 NLM ISO Abbreviation: Cell Physiol Biochem Subsets: MEDLINE
Subject
Language
English
Abstract
Background/aims: Pancreatic cancer has the poorest survival rate among all cancer types. Therefore, it is essential to develop an effective treatment strategy for this cancer.
Methods: We performed carbon ion radiotherapy (CIRT) in human pancreatic cancer cell lines and analyzed their survival, apoptosis, necrosis, and autophagy. To investigate the role of CIRT-induced autophagy, autophagy inhibitors were added to cells prior to CIRT. To evaluate tumor formation, we inoculated CIRT-treated murine pancreatic cancer cells on the flank of syngeneic mice and measured tumor weight. We immunohistochemically measured autophagy levels in surgical sections from patients with pancreatic cancer who received neoadjuvant chemotherapy (NAC) plus CIRT or NAC alone.
Results: CIRT reduced the survival fraction of pancreatic cancer cells and induced apoptotic and necrotic alterations, along with autophagy. Preincubation with an autophagy inhibitor accelerated cell death. Mice inoculated with control pancreatic cancer cells developed tumors, while those inoculated with CIRT/autophagy inhibitor-treated cells showed significant evasion. Surgical specimens of NAC-treated patients expressed autophagy comparable to control patients, while those in the NAC plus CIRT group expressed little autophagy and nuclear staining.
Conclusion: CIRT effectively killed the pancreatic cancer cells by inhibiting their autophagy-inducing abilities.
Competing Interests: The authors declare no conflicts of interest.
(© Copyright by the Author(s). Published by Cell Physiol Biochem Press.)
Methods: We performed carbon ion radiotherapy (CIRT) in human pancreatic cancer cell lines and analyzed their survival, apoptosis, necrosis, and autophagy. To investigate the role of CIRT-induced autophagy, autophagy inhibitors were added to cells prior to CIRT. To evaluate tumor formation, we inoculated CIRT-treated murine pancreatic cancer cells on the flank of syngeneic mice and measured tumor weight. We immunohistochemically measured autophagy levels in surgical sections from patients with pancreatic cancer who received neoadjuvant chemotherapy (NAC) plus CIRT or NAC alone.
Results: CIRT reduced the survival fraction of pancreatic cancer cells and induced apoptotic and necrotic alterations, along with autophagy. Preincubation with an autophagy inhibitor accelerated cell death. Mice inoculated with control pancreatic cancer cells developed tumors, while those inoculated with CIRT/autophagy inhibitor-treated cells showed significant evasion. Surgical specimens of NAC-treated patients expressed autophagy comparable to control patients, while those in the NAC plus CIRT group expressed little autophagy and nuclear staining.
Conclusion: CIRT effectively killed the pancreatic cancer cells by inhibiting their autophagy-inducing abilities.
Competing Interests: The authors declare no conflicts of interest.
(© Copyright by the Author(s). Published by Cell Physiol Biochem Press.)