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Exploiting MCF-7 Cells’ Calcium Dependence with Interlaced Therapy

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DOI: 10.4236/jct.2013.47A006    3,554 Downloads   5,088 Views   Citations

ABSTRACT

The purpose of this study is to demonstrate MCF-7 cells’ dependence on calcium for growth and to exploit that dependence to improve chemotherapy efficacy. Fura-2 fluorescence imaging shows that MCF-7 cells maintain a higher basal intracellular calcium concentration than non-tumorigenic MCF-10A cells. Blocking T-type calcium channels with mibefradil reduced MCF-7 intracellular calcium concentration. Flow cytometry shows that knocking down T-type calcium channel expression with siRNA caused an increase in MCF-7 cells in G1 phase and a decrease in cells in S phase. Proliferation assays of MCF-7 cells treated with EGTA and thapsigargin reveal the dependence of MCF-7 cell growth on extracellular and intracellular calcium sources, respectively. In vitro, interlaced treatment that alternated the T-type calcium channel blocker NNC-55-0396 with paclitaxel more effectively reduced MCF-7 cell number than chemotherapy alone. In a mouse in vivo model, interlaced mibefradil and paclitaxel more effectively reduced MCF-7 xenograft size than chemotherapy alone. These findings indicate that MCF-7 cells are dependent on calcium for proliferation, particularly in passing the G1/S cell cycle checkpoint. Further, this dependence on calcium can be exploited by alternating treatment with T-type calcium channel blockers with paclitaxel in an interlaced therapy scheme that increases the efficacy of the chemotherapy.

Conflicts of Interest

The authors declare no conflicts of interest.

Cite this paper

J. Pottle, C. Sun, L. Gray and M. Li, "Exploiting MCF-7 Cells’ Calcium Dependence with Interlaced Therapy," Journal of Cancer Therapy, Vol. 4 No. 7A, 2013, pp. 32-40. doi: 10.4236/jct.2013.47A006.

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