Effect of electroporation on radiotherapy treatment in human hepatocellular carcinoma cells

Yıl 2021, Cilt: 4 Sayı: 2, 17 - 21, 08.12.2021

Mehmet Eşref Alkış Sefa Yeşilbaş

https://doi.org/10.54565/jphcfum.1006281

Öz

Thanks to technological developments and clinical studies in recent years, radiotherapy has been widely used in cancer treatment, and radiation can be applied effectively to cancer cells without harming healthy tissues. However, some types of cancer cells are resistant to radiotherapy which can be applied at certain doses that do not harm normal tissues. In this context, the main purpose of this study is to increase the sensitivity of cancerous cells to radiotherapy and by doing so to reduce the negative side effects of radiotherapy with lower doses of radiation and to get more efficient results through the combined use of treatments. In this study, HepG2 (Human hepatocellular carcinoma) liver cancer cells were treated by ionizing radiation (210 kV x-ray at a dose rate of 2.1 Gy/min) or electroporation (1125 V/cm, 100 µs, 1 Hz, 8 square waves) or combination of these two therapies. Responses to these treatments were determined by the MTT viability test. It was observed that the survival rate of HepG2 cancer cells significantly decreased in the group treated with ionizing radiation after electroporation. The electrical pulses caused a 1.25-fold increase in the sensitivity of HepG-2 cancer cells to 210 kV x-ray. These results show that the application of electroporation before radiotherapy can significantly increase the sensitivity of HepG2 cancer cells.

Anahtar Kelimeler

Electroporation, HepG2, Ionizing radiation, Radiotherapy

Kaynakça

• M.C. Hulvat, Cancer incidence and trends, Surgical Clinics, 2020, 100, 469-481.
• P. Dasgupta, C. Henshaw, D.R Youlden, P.J. Clark, J.F. Aitken, P.D. Baade, Global Trends in Incidence Rates of Primary Adult Liver Cancers: A Systematic Review and Meta-Analysis, Frontiers in oncology, 2020, 10, 171.
• F. Bray, J. Ferlay, I. Soerjomataram, R.L. Siegel, L.A. Torre, A. Jemal, Erratum: Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries, CA Cancer J Clin, 2020, 70, 313.
• Q. Zhang, F.X. Wang, K. Jia, L. Kong, Natural product interventions for chemotherapy and radiotherapy-induced side effects, Frontiers in pharmacology, 2018, 9, 1253.
• M. Baumann, M. Krause, J. Overgaard, J. Debus, S.M. Bentzen, J. Daartz, C. Richter, D. Zips, T. Bortfeld, Radiation oncology in the era of precision medicine, Nature Reviews Cancer, 2016, 16, 234-249.
• H.H. Chen and M.T. Kuo, Improving radiotherapy in cancer treatment: Promises and challenges, Oncotarget, 2017, 8, 62742-62758.
• A. Yadollahpour, Z. Rezaee, V. Bayati, M.J.T. Birgani, and F.N. Dehbashi, Radiotherapy enhancement with electroporation in human intestinal colon cancer HT-29 cells, Asian Pacific journal of cancer prevention: APJCP, 2018, 19, 1259-1262.
• G. Serša, S. Kranjc, and M. Čemažar, Improvement of combined modality therapy with cisplatin and radiation using electroporation of tumors, International Journal of Radiation Oncology* Biology* Physics, 2000, 46, 1037-1041.
• J. Gehl, Electroporation: theory and methods, perspectives for drug delivery, gene therapy and research, Acta Physiologica Scandinavica, 2003, 177, 437-447.
• D. Rabussay, N.B. Dev, J. Fewell, L.C. Smith, G. Widera, and L. Zhang, Enhancement of therapeutic drug and DNA delivery into cells by electroporation, Journal of Physics D: Applied Physics, 2003, 36, 348-363.
• M.E. Alkış, Ü. Keleştemür, Y. Alan, N. Turan, and K. Buldurun, Cobalt and ruthenium complexes with pyrimidine based Schiff base: Synthesis, characterization, anticancer activities and electrochemotherapy efficiency, Journal of Molecular Structure, 2021, 1226, 129402.
• B. Gabriel, and J. Teissie, Generation of reactive‐oxygen species induced by electropermeabilization of Chinese hamster ovary cells and their consequence on cell viability, European Journal of Biochemistry, 1994, 223, 25-33.
• M. Cemazar, I. Hreljac, G. Sersa, and M. Filipic, Construction of EGFP expressing HepG2 cell line using electroporation, in IFMBE Proceedings, Berlin, Heidelberg: Springer Berlin Heidelberg, 2009, 128–131.
• L.G. Campana, D. Miklavčič, G. Bertino, R. Marconato, S. Valpione, I. Imarisio, M.V. Dieci, E. Granziera, M. Cemazar, and M. Alaibac, Electrochemotherapy of superficial tumors–Current status: Basic principles, operating procedures, shared indications, and emerging applications, Semin. Oncol, 2019, 46, 173–191.
• M.E. Alkış, K. Buldurun, N. Turan, Y. Alan, Ü.K. Yılmaz, and A. Mantarcı, Synthesis, characterization, antiproliferative of pyrimidine based ligand and its Ni (II) and Pd (II) complexes and effectiveness of electroporation, Journal of Biomolecular Structure Dynamics, 2020, 1-11.
• E. Grela, J. Kozłowska, and A. Grabowiecka, Current methodology of MTT assay in bacteria–A review, Acta histochemica, 2018, 120, 303-311.
• A.B. Yıldırım, E. Mutlu, and M. Yıldırım, Cytotoxic Effects of Thiazolo [3, 2-C] Pyrimidines Against Mcf-7 And Hepg2/C3a Carcinoma Cell Lines, Hacettepe Journal of Biology Chemistry, 2018, 46, 237-246.
• P. Kumar, A. Nagarajan, and P.D. Uchil, Analysis of cell viability by the MTT assay, Cold Spring Harbor Protocols, 2018, 2018, pdb. prot095505.
• K. Hara, A. Takeda, Y. Tsurugai, Y. Saigusa, N. Sanuki, T. Eriguchi, S. Maeda, K. Tanaka, and K. Numata, Radiotherapy for hepatocellular carcinoma results in comparable survival to radiofrequency ablation: a propensity score analysis, Hepatology, 2019, 69, 2533-2545.
• C. Choi, G. S. Yoo, W. K. Cho, and H. C. Park, Optimizing radiotherapy with immune checkpoint blockade in hepatocellular carcinoma, World journal of gastroenterology, 2019, 25, 2416-2429.
• Y. H. Lee, D. Tai, C. Yip, S. P. Choo, and V. Chew, Combinational Immunotherapy for Hepatocellular Carcinoma: Radiotherapy, Immune Checkpoint Blockade and Beyond, Frontiers in Immunology, 2020, 11, 568759.
• Z. Rezaee, A. Yadollahpour, and V. Bayati, Single Intense Microsecond Electric Pulse Induces Radiosensitization to Ionizing Radiation: Effects of Time Intervals Between Electric Pulse and Ionizing Irradiation, Frontiers in oncology, 2018, 8, 418.
• P. Shil, P. Vidyasagar, S. Sanghvi, and K.P. Mishra, Enhancement of cytotoxic effects of radiation and drug by electroporation in cancer cells: in vitro and in vivo studies, BARC Newslett, 2006, 273, 167-171.
• S. Kranjc, M. Cemazar, A. Grosel, M. Sentjurc, and G. Sersa, Radiosensitising effect of electrochemotherapy with bleomycin in LPB sarcoma cells and tumors in mice, BMC cancer, 2005, 5, 115.
• M.E. Alkış, N. Turan, Y. Alan, S. Irtegun Kandemir, and K. Buldurun, Effects of electroporation on anticancer activity of 5-FU and newly synthesized zinc(II) complex in chemotherapy-resistance human brain tumor cells, Med Oncol, 2021, 38, 129.
• M.E. Alki̇s, Effects of electroporation on cytotoxicity of 4-aminopyrimidin-2-(1H)-one based ligand and its Cobalt (II) and Ruthenium (II) complexes in MCF-7 cancer cells, Dicle Med J, 2021, 48, 498–506.
• H. de A. Carvalho and R. C. Villar, Radiotherapy and immune response: the systemic effects of a local treatment, Clinics, 2018, 73, e557s.