Combined Hyperthermia and Radiation Therapy for Treatment of Hepatocellular Carcinoma

Document Type: Research Articles

Authors

1 Department of Molecular Biology, Genetic Engineering and Biotechnology Research Institute (GEBRI), University of Sadat City, Egypt.

2 Cancer Biology and Genetics Laboratory, Center of Excellence for Advanced Sciences, National Research Center, Egypt.

3 Egyptian Atomic Energy Authority, Department of Radioisotope, Cairo, Egypt.

Abstract

Background: There is no doubt that hyperthermia is one of the powerful radiosensitizers. Finding a proper mechanism
working in hyperthermia/radiation combination is still pronounced challenge. Objectives: This study is focusing on
the anti-cancer activities (anti-proliferative, anti-angiogenic and antiapoptotic) of thermoradiotherapy. Materials and
Methods: Liver cancer cell line (HepG2) was treated by 37oC, 40oC and 43oC hyperthermia degrees combined with
three radiation doses (2 Gy, 4 Gy and 8 Gy) for 24, 48 and 72 hrs. Cell viability, apoptotic/necrotic cell screening,
apoptotic (BAX and FasL) and antiapoptotic (BCL-2 and GRP78) genes, and pro-angiogenic mediators [vascular
endothelial- (VEGF) and Platelet derived-growth factors (PDGF) ware investigated. Results: Our data showed that 40oC
temperature combined with 4 Gy radiation gives a significant decrease (p<0.05) in cell viability. Maximum cytotoxicity
was reported 48 hr post-treatment followed by slight restoration of cell viability after 72 hr. Compared with untreated
cells, only 5% of viable cells with a high percentage of apoptotic (31%) and necrotic (63%) cells were demonstrated
in 40oC/4 Gy/48 hr group. Expression of pro-apoptotic genes (BAX and FasL) were increased after hyperthermia with
apparent elevation in 40oC/4 Gy/48 hr group coincides with moderate expression of antiapoptotic BCL-2 and GRP78
genes. A significant reduction (p<0.001; p<0.05) in VEGF and PDGF levels; respectively was shown at 40oC/4 Gy/48
hr group. Conclusions: This pilot study proposed 40oC mild temperature hyperthermia as a favorable hyperthermal
condition with 4 Gy radiotherapy in HCC treatment. A further research has to be performed considering an application
of more than one session of radiothermal therapy at 40oC/4 Gy for total abrogation of cancer cells.

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