Treatment of cervical cancer by electrochemotherapy with bleomycin, cisplatin, and calcium: an in vitro experimental study.

Abstract

Low-dose chemotherapy in advanced stages of cancer does not give a positive response in treatment. The use of high-dose antineoplastic drugs creates significant side effects. The limiting situation in treatment creates a need for new generation drugs with less side effects and new treatment methods that will enable low-dose drug use. Electroporation (EP), a phenomenon, is a technique in which the membrane permeability is increased by the establishment of hydrophilic pores in the cell membrane with short and high-voltage electrical pulses. In the present investigation study, we aimed to inspect the effects of EP plus bleomycin, cisplatin, and calcium administration (CaEP) on cell viability, apoptotic activity, gene expression p53, Bax/Bcl-2 rate mitochondrial membrane potential (ΔΨm), and cell cycle in HeLa cervical cancer cell line. The permeabilization of the membrane was evaluated in flow cytometry with the PI method, and cell viability was measured in an ELISA reader with the WST-8 method. For bleomycin and cisplatin doses applied to HeLa cells, the concentration values (IC50) that inhibited 50% of the cells were found to be 214.11 ± 4.7µM and 35.16 ± 3.3µM, respectively. The IC50 values of the groups administered together with EP were calculated as 0.44 ± 0.3µM for bleomycin and 20.55 ± 4.3µM for cisplatin. There was no change in cell viability in calcium alone application, but a statistically notable reduction in cell vitality was observed in CaEP application. An increase in ΔΨm was found in bleomycin and CaEP exposure with EP. It was determined that EP exposure caused G0/G1 arrest in the cell cycle at all electric field intensities. It was determined that EP application in HeLa cells increased bleomycin cytotoxicity 487 times and cisplatin cytotoxicity 1.71 times, and CaEP could be an alternative treatment method.