Effects of carbon ion beam alone or in combination with cisplatin on malignant mesothelioma cells in vitro

Our plain-English summary of Effects of carbon ion beam alone or in combination with cisplatin on malignant mesothelioma cells in vitro, by S. Sai, M. Suzuki, E.H. Kim, et al (Oncotarget, 2018).

The study

• Authors: S. Sai, M. Suzuki, E.H. Kim, M. Hayashi, G. Vares, N. Yamamoto, T. Miyamoto
• Journal: Oncotarget
• Published: 2018;9(19):14849-14861
• Cited by: 17 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

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.

In plain English

This laboratory study tested carbon ion beam radiation, alone or with the chemotherapy drug cisplatin, on two human mesothelioma cell lines, MESO1 and H226, grown in dishes. X-rays were used for comparison. The study did not involve asbestos or patients. Carbon ion beams alone reduced cell viability, and adding 25 µM cisplatin reduced it further. The doses needed to cut cell survival to 10% with X-rays were 5.04 Gy for MESO1 and 5.44 Gy for H226. With the carbon ion beam at 73 keV/μm they were 1.72 Gy and 1.93 Gy. Relative to X-rays, that beam's effectiveness values were 2.93 and 2.82. The share of cells marked as cancer stem-like (CD44+/CD26+) rose after X-rays but not after carbon ions. Combined carbon ion and cisplatin treatment increased signs of cell death (apoptosis), autophagy-related gene expression, and DNA damage foci more than single treatments. The authors concluded that cisplatin with carbon ion beams may have the potential to maximize carbon ion radiotherapy's effects for mesothelioma. They said further laboratory and animal studies are needed to examine the genes at the protein level.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory (in vitro) cell-culture experiment
• Who was studied: Two human mesothelioma cell lines, H226 and MESO1, bought from the American Type Culture Collection, including cancer stem-like (CD44+/CD26+) and other (CD44–/CD26–) cells sorted from them. No people or animals were studied.
• Exposure: Carbon ion beams from the HIMAC accelerator (initial energy 290 MeV/n; dose-averaged LET values of 13, 50 and 73 keV/μm), alone or with cisplatin (12.5, 25 or 50 µM, mainly 25). Conventional 200 kVp X-rays were the comparison. No asbestos exposure was studied.
• Main results:
  • In both MESO1 and H226 cells, viability fell after carbon ion beam alone and fell more when combined with 25 µM cisplatin.
  • The dose that reduced survival to 10% was, for MESO1 (H226), 5.04 (5.44) Gy for X-rays, 4.24 (4.46) Gy for carbon ions at 13 keV/μm, and 1.72 (1.93) Gy for the higher-LET carbon ion beam. The table gives that beam as 73 keV/μm; this sentence of the text says 70 keV/μm.
  • Relative biological effectiveness compared with X-rays, for MESO1 (H226) cells: 1.19 (1.22) at 13 keV/μm and 2.93 (2.82) at 73 keV/μm.
  • Out of 500 plated cells, CD44+/CD26+ cells from MESO1 and H226 formed 25 and 40 colonies, against 12 and 14 colonies for CD44–/CD26– cells (p < 0.01).
  • In MESO1 cells, the proportion of cancer stem-like CD44+/CD26+ cells rose with X-ray dose but did not change after carbon ion irradiation. H226 cells showed a similar pattern.
  • Carbon ions plus cisplatin shrank spheroid size more than X-rays alone, carbon ions alone, or X-rays plus cisplatin.
  • In CD44+/CD26+ cells from MESO1, carbon ions alone or with cisplatin increased the apoptosis-related gene BAX and decreased Bcl2 (p < 0.01).
  • In CD44+/CD26+ cells from MESO1, the combination increased the autophagy-related genes Beclin1 and ATG7 (p < 0.01).
  • Caspase 3/7 activity, a marker of apoptosis, rose with carbon ion dose and rose further when cisplatin was added.
  • Carbon ions alone at 1 Gy significantly increased apoptosis.
  • In MESO1 cells, carbon ions combined with cisplatin blocked cell cycle progression (sub-G1 arrest).
  • In CD44+/CD26+ cells from MESO1, more and larger γH2AX foci (markers of DNA double-strand breaks) remained 24 h after the combination than after carbon ions alone.
• The authors' conclusion: The authors concluded that cisplatin combined with carbon ion beams may have the potential to maximize the therapeutic effects of carbon ion radiotherapy for malignant mesothelioma.
• Limitations the authors state:
  • Gene findings were at the mRNA level only. Further laboratory and animal studies are needed to examine the genes at the protein level.

Topics

Medical terms in this study, explained in our Lexicon: Cisplatin, Mesothelioma, Apoptosis, STEM.

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