The effectiveness of chemotherapy and electrochemotherapy on ovarian cell lines in vitro

Abstract

The presented study aimed to evaluate in vitro the effectiveness of improvement standard chemotherapy with bleomycin by electroporation in two various ovarian cancer cell lines. Two human ovarian cell lines OvBH-1 and SKOV-3 were used. The lines were selected because of their resistance to several therapeutic methods. As anticancer drug we use range of concentrations of bleomycin. In EP and ECT experiments different voltage values: from 0 to 1200 V/cm, 8 pulses with duration of 100μs and intervals between pulses 1s long were used. The cells viability after applied treatments was evaluated by MTT assay. The expression of heat shock proteins - HSP27 was examined by immunocytochemical ABC method.The cytotoxicity with different concentrations of bleomycin alone was not significantly decrease in both cell lines. It confirms resistance of these cells to conventional chemotherapy. The highest decrease of cell proliferation was observed after EP with bleomycin after 48h of incubation for 1000 V/cm. The intensity of expression of small heat shock proteins HSP27 slightly increased after ECT in both treated cell lines, in particular in OvBH-1. The presented study indicated that application of electroporation may effectively enhance chemotherapy with bleomycin, particularly in the case of treating ovarian cancer resistant to standard therapy.

Recent Advances in Electrochemotherapy

“…2,14,18 Thus, electrochemotherapy is still evaluated in different types of cancer, either in vitro or in vivo, including colon carcinoma CT26 (in vitro) 19 ; bladder cancer SW780 (in vitro and in vivo) 20 ; fibroblasts, human umbilical vein endothelial cells (HUVEC; in vitro) and two squamous cell carcinomas, CAL-27 and SCC-4 (in vitro) 21 ; ovarian cell lines OvBH-1 and SKOV-3 (in vitro) 22 ; human neuroblastoma SH-SY5Y cells (in vitro) 23 ; BRAF-mutated melanoma cells (SK-MEL-28) and their counterpart without mutation, CHL-1 cells (in vitro) 24 ; chemoresistant uveal melanoma cells (Mel 270, 92-1, OMM-1, OMM-2) (in vitro) 25 ; primary cells from metastatic pancreatic tumors (in vitro) 26 ; human papillomavirus (HPV)-positive head and neck squamous cell carcinoma 2A3 (in vitro and in vivo) 27 ; Lewis lung carcinoma and CT 25 colorectal carcinoma (in vivo) 28 ; conjunctival melanoma CRMM1 and CRMM2 and normal conjunctival epithelial cells HCjE-Gi (in vitro) 29 ; radioresistant head and neck squamous cell carcinoma Fa-DuRR (in vitro and in vivo) 30 ; and small cell lung cancer H69AR cells (in vitro). 31 In general, it was demonstrated that electrochemotherapy with bleomycin or cisplatin causes immunogenic cell death in colon carcinoma 19,28 ; that human endothelial cells are more susceptible to electrochemotherapy than tumor cells, 21 supporting the antivascular effect in vivo; that electrochemotherapy is effective in ovarian carcinoma cells resistant to standard therapy 22 ; and that electrochemotherapy is also effective in neuroblastoma and primary pancreatic tumor cells, which was not demonstrated before. 23,26 Furthermore, it was demonstrated that electrochemotherapy with cisplatin is a promising therapeutic approach for bladder cancer 20 and that it is more effective in HPV-positive than HPV-negative head and neck tumors.…”

The Impact of Extracellular Ca2+ and Nanosecond Electric Pulses on Sensitive and Drug-Resistant Human Breast and Colon Cancer Cells

“…The available literature shows that physical methods, e.g., ultrasonic techniques (sonoporation) [13,14] or electroporation [15][16][17] in combination with chemotherapy, or electromagnetic treatment against antibiotic [18] or antimicrobial resistance [19], can be efficiently applied to overcome cell resistance in vivo and in vitro. Electrochemotherapy is based on the application of high-voltage electric pulses, causing permeabilization of membranes (electroporation) and increased drug uptake by cancer cells [20]. It is a pulse-dependent phenomenon, and usually, the microsecond range pulses are used [21].…”

Electrochemotherapy Using Doxorubicin and Nanosecond Electric Field Pulses: A Pilot in Vivo Study

“…Among the most established applications of electroporation is the treatment of cancer [ 4 ]. This allows the minimization of the dosage of chemotherapeutic drugs [ 5 , 6 ] and/or adverse effects during the ablation of the tumor [ 7 ]. Consequently, the combination of chemotherapeutic drugs and electroporation was coined electrochemotherapy and is widely used in clinics [ 8 ].…”