Enhanced breast cancer therapy with nsPEFs and low concentrations of gemcitabine

Cancer Cell International

Stephen J Beebe¹  Jing Fang³  Jue Zhang²  Wendong Wei³  Jinsong Guo³  Shan Wu³ 

[1] Frank Reidy Research Center for Bioelectrics, Old Dominion University, 4211 Monarch Way, Suite 300, Norfolk 23508, VA, USA;Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China;College of Engineering, Peking University, Beijing 100871, China

关键词: Necrosis (necroptosis);    Apoptosis;    Clonogenics;    Synergism;    Gemcitabine;    Non-thermal;    Nanosecond pulsed electric fields (nsPEFs);    MDA-MB-231;    MCF-7;    Breast cancer;   

Others  :  1121648
DOI  :  10.1186/s12935-014-0098-4

 received in 2014-05-12, accepted in 2014-09-17,  发布年份 2014

【 摘 要 】

Background

Chemotherapy either before or after surgery is a common breast cancer treatment. Long-term, high dose treatments with chemotherapeutic drugs often result in undesirable side effects, frequent recurrences and resistances to therapy.

Methods

The anti-cancer drug, gemcitabine (GEM) was used in combination with pulse power technology with nanosecond pulsed electric fields (nsPEFs) for treatment of human breast cancer cells in vitro. Two strategies include sensitizing mammary tumor cells with GEM before nsPEF treatment or sensitizing cells with nsPEFs before GEM treatment. Breast cancer cell lines MCF-7 and MDA-MB-231 were treated with 250 65 ns-duration pulses and electric fields of 15, 20 or 25 kV/cm before or after treatment with 0.38 μM GEM.

Results

Both cell lines exhibited robust synergism for loss of cell viability 24 h and 48 h after treatment; treatment with GEM before nsPEFs was the preferred order. In clonogenic assays, only MDA-MB-231 cells showed synergism; again GEM before nsPEFs was the preferred order. In apoptosis/necrosis assays with Annexin-V-FITC/propidium iodide 2 h after treatment, both cell lines exhibited apoptosis as a major cell death mechanism, but only MDA-MB-231 cells exhibited modest synergism. However, unlike viability assays, nsPEF treatment before GEM was preferred. MDA-MB-231 cells exhibited much greater levels of necrosis then in MCF-7 cells, which were very low. Synergy was robust and greater when nsPEF treatment was before GEM.

Conclusions

Combination treatments with low GEM concentrations and modest nsPEFs provide enhanced cytotoxicity in two breast cancer cell lines. The treatment order is flexible, although long-term survival and short-term cell death analyses indicated different treatment order preferences. Based on synergism, apoptosis mechanisms for both agents were more similar in MCF-7 than in MDA-MB-231 cells. In contrast, necrosis mechanisms for the two agents were distinctly different in MDA-MB-231, but too low to reliably evaluate in MCF-7 cells. While disease mechanisms in the two cell lines are different based on the differential synergistic response to treatments, combination treatment with GEM and nsPEFs should provide an advantageous therapy for breast cancer ablation in vivo.

【 授权许可】

   
2014 Wu et al.; licensee BioMed Central Ltd.

【 图 表 】

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