Synergistic growth suppression induced in esophageal squamous cell carcinoma cells by combined treatment with docetaxel and heavy carbon-ion beam irradiation

Abstract

Abstract. Heavy carbon-ion beam therapy has revealed several potential advantages over X-rays. Heavy-ion therapy has been applied for various solid tumors including esophageal squamous cell carcinoma (SCC). Although the local control rate of carbon ion radiotherapy for esophageal cancer has revealed better rates than that of conventional radiotherapy, some patients have shown resistance to the treatment. No study has evaluated whether anti-cancer drugs can enhance the anti-tumor effect of heavy carbon-ion beam irradiation. Therefore, we evaluated the efficacy of docetaxel, fluorouracil, cisplatinum, doxorubicin and gemcitabine to enhance the anti-tumor effects of heavy carbon-ion beam irradiation on human esophageal SCC cells in both in vitro and in vivo experiments. Fluorouracil, cisplatinum, doxorubicin and gemcitabine showed only additive anti-tumor effects. On the other hand, growth suppression was significantly potentiated by the combined treatment with heavy carbon-ion beam and docetaxel as compared to that treated with either agent alone. These data suggest that heavy carbon-ion beam irradiation combined with docetaxel may be a potentially useful therapeutic strategy for locally advanced esophageal SCC.

Relative Biological Effectiveness of Carbon Ions for Local Tumor Control of a Radioresistant Prostate Carcinoma in the Rat

“…Most of our present knowledge about tolerance doses and dose dependence of RBEs was derived from experiments with mouse skin (22) and jejunum (23), as well as from rat brain and spinal cord (24)(25)(26)(27). Carbon ion effects in experimental solid tumors are addressed by only a few studies using human tumor cell line xenotransplants or syngeneic mouse models with tumor growth inhibition as biological endpoint (28)(29)(30)(31).…”

Mitotic catastrophe is a putative mechanism underlying the weak correlation between sensitivity to carbon ions and cisplatin

“…Thus, it is possible that concomitant use of cisplatin will also increase the efficacy of carbon ion radiotherapy. However, preclinical data regarding the combined effect of carbon ions and cisplatin are limited; only a few small-scale studies have been conducted (Supplementary Table 1)78910. Data from these studies are unclear as to whether the cell killing effect of carbon ions plus cisplatin is synergistic.…”

“…The combined effect of X-rays and cisplatin has been extensively studied in the preclinical setting; however, there are no firm conclusions as to whether the effects are synergistic or purely additive because results vary widely from marked synergism to none at all (Supplementary Table 1)89101112131415161718192021. Furthermore, the presence/absence of synergism is inconsistent even between studies using the same cell lines (i.e., Agoni et al vs. Flentje et al .…”

Upregulation of stress-response genes with cell cycle arrest induced by carbon ion irradiation in multiple murine tumors models

“…[5][6][7][8][9] The main disadvantage of this approach is the lack of correlation to the tumor microenvironment and hence the clinical setting. 10 Other disadvantages include significant differences in the gene expression profile between cell lines in vitro and the same cell lines growing in vivo and the effect of other factors related to the cellular microenvironment on the gene expression profile.…”