Biological characteristics of gene expression features in pancreatic cancer cells induced by proton and X-ray irradiation

Abstract

Background: Radiation therapy is an important alternative treatment for advanced cancer. The aim of the current study was to disclose distinct alterations of the biological characteristics of gene expression features in pancreatic cancer cells, MIAPaCa-2, following proton and X-ray irradiation.

Materials and methods: Using cDNA microarray, we examined the gene expression alterations of MIAPaCa-2 cells following proton or X-ray irradiation. We also isolated the surviving MIAPaCa-2 cells after irradiation and analyzed their gene expression profiles.

Results: Although the cytocidal effects of both types of irradiation were similar at sufficient doses in vitro and in vivo, the affected gene expression profile alterations of MIAPaCa-2 cells irradiated with protons were distinct from those irradiated with X-ray. Interestingly, clustering analysis of gene expression of the surviving MIAPaCa-2 cells was also completely discernible between the two types of irradiation. However, a similar cytocidal effect was still observed in the proton- and X-ray-irradiated surviving cells after re-irradiation, commonly showing biological effects related to apoptosis and cell cycle processes.

Conclusions: Proton irradiation treatment for pancreatic cancer provides the distinct biological effect of steady gene expression alterations compared to X-ray irradiation; however, surviving cells from both types of irradiation were still susceptible to the cytocidal effects induced by proton re-irradiation treatment.

Keywords:

• Proton
• X-ray
• irradiation
• gene expression profile
• pancreatic cancer

Acknowledgments

We would like to thank Ms. Sachie Yamazaki for her excellent technical assistance.

Disclosure statement

No potential conflict of interest was reported by the authors.

Notes on contributors

Haruo Fujinaga, MD, is awaiting conferral of a PhD in Medical Sciences from Kanazawa University. His research was developed within the department of Disease control and homeostasis, Kanazawa University, Graduate school of medical sciences, and focusses on radio- and proton-therapies of tumors of the gastrointestinal tract.

Associate Professor Yoshio Sakai, MD, PhD., is a gastroenterologist working in the Department of Gastrroenterology, Kanazawa University.

Associate Professor Tatsuya Yamashita, MD, PhD, is working in the Department of Gastroenterology, Kanazawa University Hospital, focussing his research in hepatology research. He worked at Global Hepatitis Programme in WHO Headquarters as first secondee from Kanazawa University. He contributed to parts of algorithm and monitoring for drug toxicity in WHO HBV guidelines.

Associate Professor Kuniaki Arai, MD, PhD, is working in the Department of Gastroenterology, Kanazawa University Hospital, focussing his research on the treatments of hepatocellular carcinoma with radiofrequency ablation (RFA) and chemotherapy.

Associate Professor Takeshi Terashima, MD, PhD, is working in the Department of Gastroenterology, Kanazawa University Hospital, focussing his research in hepatology research.

Takuya Komura, MD, PhD, is working in the department of System Biology, Kanazawa University. His expertise is in gastroenterology, infectious diseases and surgery.

Akihiro Seki, MD, PhD, is a Post-Doctoral Fellow studying the role of the microbiome in affecting dendritic cell function. He started his clinical practice as gastroenterologist, and his basic science career at the Graduate School of Medical Science, Kanazawa University, Japan. He obtained his PhD in Medical Science at the Kanazawa University.

Assistant Professor Kazunori Kawaguchi, MD, PhD, is working as physician and researcher in the Department of Gastroenterology, Kanazawa University Hospital, focussing on viral hepatitis and liver regeneration therapies. He worked as Research Fellow in the National Institute of Allergy and Infectious Diseases (NIAID).

Alessandro Nasti, MPharm, PhD, is working as Postdoctoral Researcher in the in the department of System Biology, Kanazawa University. His basic research is focussed on immunotherapies for the diseases of the gastrointestinal tract.

Keiko Yoshida, MSc, is enrolled as PhD student in the department of Disease control and homeostasis, Kanazawa University. Her basic research is focussed on the development of new chemoimmunotherapies for pancreatic ductal adenocarcinomas.

Professor Takashi Wada, MD, PhD, is Head of Department of Nephrology and Laboratory Medicine, Kanazawa University Hospital. He specializes in Nephrology, Laboratory Medicine and Internal Medicine with a focus in Nephrology Clinical immunology, therapeutic application of novel anti-inflammatory drugs and development of novel laboratory medicine and biomarkers.

Kazutaka Yamamoto, MD, PhD, is a radiation oncologist as well as a basic radiologist. He worked for The Wakasa Wan Energy Research Center, Tsuruga, Japan, as a leading researcher of particle therapy in addition to his former carrier in PET diagnosis of nuclear medicine.

Kyo Kume, PhD, is a chief researcher as well as a medical physicist at the Proton Medical Researcher Division, The Wakasa Wan Energy Research Center, Tsuruga, Japan, focusing on radiation and medical physics, especially in the field of particle therapy and beam application engineering.

Takashi Hasegawa is a research member of The Wakasa Wan Energy Research Canter, Tsuruga, Japan, focusing on accelerator engineering.

Takushi Takata, PhD, was a research member of The Wakasa Wan Energy Research Center, Fukui, Japan, focusing on particle therapy in medical physics.

Professor Masao Honda, MD, PhD is affiliated to the Faculty of Health Sciences, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University. He specializes in Liver Disease Gastroenterology, Collagenous pathology/Allergology, Virology with a focus on viral hepatitis and the molecular biology of hepatocellular carcinoma.

Professor Shuichi Kaneko, MD, PhD, is affiliated to the Faculty of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University. He specializes in Experimental Pathology, Gastroenterology, Virology, and Cancer, with a focus on Cancer Research, Liver metabolism and systemic illness, and Viral Hepatitis.