Next Article in Journal
Prenylated Flavonoids from Roots of Glycyrrhiza uralensis Induce Differentiation of B16-F10 Melanoma Cells
Next Article in Special Issue
Robotic Stereotactic Radiosurgery in Melanoma Patients with Brain Metastases under Simultaneous Anti-PD-1 Treatment
Previous Article in Journal
Intrathecal Injection of Dual Zipper Kinase shRNA Alleviating the Neuropathic Pain in a Chronic Constrictive Nerve Injury Model
Previous Article in Special Issue
In Vivo Irradiation of Mice Induces Activation of Dendritic Cells
Open AccessArticle

Enhancement of Radiation Effectiveness in Cervical Cancer Cells by Combining Ionizing Radiation with Hyperthermia and Molecular Targeting Agents

1
Laboratory of Experimental Oncology and Radiobiology, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105AZ Amsterdam, The Netherlands
2
Center for Experimental Molecular Medicine, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105AZ Amsterdam, The Netherlands
3
Department of Radiation Oncology, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105AZ Amsterdam, The Netherlands
4
Department of Medical Biology, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105AZ Amsterdam, The Netherlands
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2018, 19(8), 2420; https://doi.org/10.3390/ijms19082420
Received: 27 July 2018 / Revised: 15 August 2018 / Accepted: 15 August 2018 / Published: 16 August 2018
(This article belongs to the Special Issue Partnership of Radiotherapy and Immunotherapy)
Hyperthermia (HT) and molecular targeting agents can be used to enhance the effect of radiotherapy (RT). The purpose of this paper is to evaluate radiation sensitization by HT and different molecular targeting agents (Poly [ADP-ribose] polymerase 1 inhibitor, PARP1-i; DNA-dependent protein kinase catalytic subunit inhibitor, DNA-PKcs-i and Heat Shock Protein 90 inhibitor, HSP90-i) in cervical cancer cell lines. Survival curves of SiHa and HeLa cells, concerning the combined effects of radiation with hyperthermia and PARP1-i, DNA-PKcs-i or HSP90-i, were analyzed using the linear-quadratic model: S(D)/S(0) = exp − (αD + βD2). The values of the linear-quadratic (LQ) parameters α and β, determine the effectiveness at low and high doses, respectively. The effects of these sensitizing agents on the LQ parameters are compared to evaluate dose-dependent differences in radio enhancement. Combination of radiation with hyperthermia, PARP1-i and DNA-PKcs-i significantly increased the value of the linear parameter α. Both α and β were significantly increased for HSP90-i combined with hyperthermia in HeLa cells, though not in SiHa cells. The Homologous Recombination pathway is inhibited by hyperthermia. When hyperthermia is combined with DNA-PKcs-i and PARP1-i, the Non-Homologous End Joining or Alternative Non-Homologous End Joining pathway is also inhibited, leading to a more potent radio enhancement. The observed increments of the α value imply that significant radio enhancement is obtained at clinically-used radiotherapy doses. Furthermore, the sensitizing effects of hyperthermia can be even further enhanced when combined with other molecular targeting agents. View Full-Text
Keywords: radiation sensitization; radio enhancement, linear-quadratic model; hyperthermia; PARP1-i; DNA-PKcs-i; HSP90-i radiation sensitization; radio enhancement, linear-quadratic model; hyperthermia; PARP1-i; DNA-PKcs-i; HSP90-i
Show Figures

Figure 1

MDPI and ACS Style

IJff, M.; Van Oorschot, B.; Oei, A.L.; Krawczyk, P.M.; Rodermond, H.M.; Stalpers, L.J.A.; Kok, H.P.; Crezee, J.; Franken, N.A.P. Enhancement of Radiation Effectiveness in Cervical Cancer Cells by Combining Ionizing Radiation with Hyperthermia and Molecular Targeting Agents. Int. J. Mol. Sci. 2018, 19, 2420.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop