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. 2019 Aug 20:19:52-58.
doi: 10.1016/j.ctro.2019.08.003. eCollection 2019 Nov.

Overcoming radioresistance in WiDr cells with heavy ion irradiation and radiosensitization by 2-deoxyglucose with photon irradiation

Felix Christian Hasse  1 , Stefan Alexander Koerber  1 , Elena Sophie Prigge  2 , Jakob Liermann  1 , Magnus von Knebel Doeberitz  2 , Juergen Debus  1 , Florian Sterzing  1
Affiliations

Overcoming radioresistance in WiDr cells with heavy ion irradiation and radiosensitization by 2-deoxyglucose with photon irradiation

Felix Christian Hasse et al. Clin Transl Radiat Oncol. .

Abstract

Background and purpose: Radiosensitizers and heavy ion irradiation could improve therapy for female patients with malignant tumors located in the pelvic region through dose reduction. Aim of the study was to investigate the radiosensitizing potential of 2-deoxy-d-glucose (2-DG) in combination with carbon ion-irradiation (12C) in representative cell lines of cancer in the female pelvic region.

Materials and methods: The human cervix carcinoma cell line CaSki and the colorectal carcinoma cell line WiDr were used. 2-DG was employed in two different settings, pretreatment and treatment simultaneous to irradiation. Clonogenic survival, α and β values for application of the linear quadratic model and relative biological effectiveness (RBE) were determined. ANOVA tests were used for statistical group comparison. Isobolograms were generated for curve comparisons.

Results: The comparison of monotherapy with 12C versus photons yielded RBE values of 2.4 for CaSki and 3.5 for WiDr along with a significant increase of α values in the 12C setting. 2-DG monotherapy reduced the colony formation of both cell lines. Radiosensitization was found in WiDr for the combination of photon irradiation with synchronous application of 2-DG. The same setup for 12C showed no radiosensitization, but rather an additive effect. In all settings with CaSki, the combination of irradiation and 2-DG exhibited additive properties.

Conclusion: The combination of 2-DG and photon therapy, as well as irradiation with carbon ions can overcome radioresistance of tumor cells such as WiDr.

Keywords: Antimetabolites; Cell survival; Deoxyglucose; Heavy ion radiotherapy; Pelvis; Photons; Radiation-sensitizing agents; Relative biological effectiveness.

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Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Fig. 1
Fig. 1
Clonogenic survival after irradiation with 12C or photons. CaSki left and WiDr right. Symbols represent experimental data with their standard deviations, lines are results of the fit described in the text.
Fig. 2
Fig. 2
Clonogenic survival after 2-DG monotherapy. CaSki left and WiDr right. Symbols represent experimental data with their standard deviations, the lines are visual guides.
Fig. 3
Fig. 3
Comparison of clonogenic survival between low dose 2-DG as a pretreatment to photon therapy and synchronous combination therapy. Results for CaSki (left) and WiDr (right). Doses were 0.1 mM and 0.7 mM, respectively. Symbols represent experimental data with their standard deviations, the lines are results of the fit described in the text.
Fig. 4
Fig. 4
Comparison of clonogenic survival between synchronous combination therapy of high dose 2-DG with photon irradiation in WiDr and the matching isobologram. Symbols represent experimental data with their standard deviations, the lines are results of the fit described in the text.
Fig. 5
Fig. 5
Comparison of clonogenic survival between synchronous combination therapy of low dose 2-DG with photon and carbon ion irradiation. CaSki left and WiDr right. Symbols represent experimental data with their standard deviations, the lines are results of the fit described in the text.
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