Bcl - 2 confers survival in cisplatin treated cervical cancer cells : circumventing cisplatin dose - dependent toxicity and resistance
Date
2015
Authors
Leisching, Gina
Loos, Benjamin
Botha, Matthys
Engelbrecht, Anna‑Mart
Journal Title
Journal ISSN
Volume Title
Publisher
BioMed Central
Abstract
Abstract
Background: Cisplatin is the main chemotherapeutic drug for the treatment of cervical cancers, however resistance
to cisplatin is increasingly common and therefore has limited the efficacy and use of this drug in the clinic. Dosedependent
toxicity poses an additional challenge since patients suffer long-term and often permanent side-effects
after treatment. Bcl-2 up-regulation has been implicated in the resistance to cisplatin in a variety of cancer cell lines,
however its role in cervical cancer is confounding.
Methods: A low, non-cytotoxic concentration of cisplatin was used in the treatment of HeLa and CaSki cells. Bcl-2
expression was determined through Western blotting and immunocytochemistry before and after treatment with
cisplatin. To assess the reliance of the cervical cancer cells on Bcl-2 in the presence of cisplatin, Bcl-2 knock-down was
achieved through RNA interference, where after apoptosis was assessed through PARP cleavage (Western blotting),
Caspase activity (Caspase-Glo©) and PI inclusion analysis (Flow cytometry). Finally, pre-malignant and malignant cervi‑
cal tissue was analysed for the presence of Bcl-2 through Western blotting and immunofluorescence.
Results: Cervical cancer cells upregulate Bcl-2 when treated with a non-cytotoxic concentration of cisplatin, which
when silenced, effectively enhanced cisplatin sensitivity, and therefore significantly induced apoptosis. Analysis of the
expression profile of Bcl-2 in cervical tissue revealed its up-regulation in cervical carcinoma, which agrees with results
obtained from the in vitro data.
Conclusions: Our data strongly suggest that utilising a lower dose of cisplatin is feasible when combined with Bcl-2
silencing as an adjuvant treatment, thereby improving both the dose-dependent toxicity, as well as cervical cancer
resistance.
Keywords: Bcl-2, Beclin-1, Cisplatin, Cervical cancer, Apoptosis
Description
Publication of this article was funded by the Stellenbosch University Open Access Fund.
Keywords
Bcl ‑ 2, Beclin ‑ 1, Cisplatin, Cervical cance, Apoptosis
Citation
Leisching, G., Loos, B., Botha, M., Engelbrecht, A. 2015. Bcl - 2 confers survival in cisplatin treated cervical cancer cells : circumventing cisplatin dose - dependent toxicity and resistance. Journal of translational medicine, 13(328), DOI 10.1186/s12967-015-0689-4