Effects of carbon ion beam alone or in combination with cisplatin on malignant mesothelioma cells in vitro
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Sei Sai1, Masao Suzuki1, Eun Ho Kim2, Mitsuhiro Hayashi3, Guillaume Vares4, Naoyoshi Yamamoto5 and Tadaaki Miyamoto6
1Department of Basic Medical Sciences for Radiation Damages, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan
2Division of Applied Radiation Bioscience, Korea Institute of Radiological and Medical Sciences, Gongneung-dong, Nowon-Gu, Seoul, South Korea
3Breast Center, Dokkyo Medical University Hospital, Mibu-machi, Shimotsuga-gun, Tochigi, Japan
4Okinawa Institute of Science and Technology (OIST), Advanced Medical Instrumentation Unit, Onna-son, Okinawa, Japan
5Hospital of the National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Sciences and Technology, Chiba, Japan
6Chiba Foundation for Health Promotion and Disease Prevention, Chiba, Japan
Sei Sai, email: [email protected]
Masao Suzuki, email: [email protected]
Keywords: heavy-ion radiation; mesothelioma; cisplatin
Received: January 17, 2017 Accepted: December 15, 2017 Epub: December 29, 2017 Published: March 13, 2018
Malignant mesothelioma (MM) is extremely aggressive and a typical refractory cancer. In this study we investigated how effective on killing MM cells by carbon ion beam alone or in combination with cisplatin (CDDP) in vitro. Carbon ion beam (at the center of SOBP with 50 keV/μm of average LET) dose-independently suppressed MM cells MESO-1 and H226 cell viability and in combination with CDDP (25 μM) significantly enhanced its action. Relative biological effectiveness (RBE) values at 73 keV/μm and 13 keV/μm portion of carbon ion beam was estimated as 2.82-2.93 and 1.19-1.22 at D10 level relative to X-ray, respectively by using colony formation assay. Quantitative real time PCR analysis showed that expression of apoptosis-related BAX and autophagy-related Beclin1 and ATG7 was significantly enhanced by carbon ion beam alone or in combination with CDDP. Apoptosis analysis showed that caspase 3/7 activity and the percentage of apoptotic cells was dose-dependently increased after carbon ion beam and it was further increased when combined with CDDP. Spheroid formation ability of cancer stem like CD44+/CD26+ cells was significantly inhibited by carbon ion beam combined with CDDP. Besides, carbon ion beam combined with cisplatin significantly inhibited cell cycle progression (sub-G1 arrest) and induced more large number of γH2AX foci. In conclusion, carbon ion beam combined with CDDP has superior potential to kill MM cells including CSCs with enhanced apoptosis.
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