Document Type: Research Articles
Department of Molecular Biology, Genetic Engineering and Biotechnology Research Institute (GEBRI), University of Sadat City, Egypt.
Cancer Biology and Genetics Laboratory, Center of Excellence for Advanced Sciences, National Research Center, Egypt.
Egyptian Atomic Energy Authority, Department of Radioisotope, Cairo, Egypt.
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.