The role of Six1 signaling in paclitaxel-dependent apoptosis in MCF-7 cell line

  • Marzieh Armat Drug Applied Research Center and Department of Medical Biotechnology, Tabriz University of Medical Sciences
  • Taiebeh Oghabi Bakhshaiesh Drug Applied Research Center and Department of Medical Biotechnology, Tabriz University of Medical Sciences
  • Mehdi Sabzichi Students Research Committee and Department of Biochemistry and Clinical Laboratories, Tabriz University of Medical Sciences
  • Dariush Shanehbandi Department of Immunology, and Immunology Research Center, Tabriz University of Medical Sciences
  • Simin Sharifi Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Tabriz University of Medical Sciences
  • Ommoleila Molavi Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Tabriz University of Medical Sciences
  • Jamal Mohammadian 1Drug Applied Research Center, and Department of Medical Biotechnology, Tabriz University of Medical Sciences
  • Mohammad Saeid Hejazi Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Tabriz University of Medical Sciences
  • Nasser Samadi Drug Applied Research Center, Faculty of Medicine, Tabriz University of Medical Sciences
Keywords: Six1, P53, apoptosis, MCF-7, paclitaxel-resistant cells

Abstract

The resistance of cancer cells to chemotherapeutic agents represents the main problem in cancer treatment. Despite intensive research, mechanisms of resistance have not yet been fully elucidated. Six1 signaling has an important role in the expansion of progenitor cell populations during early embryogenesis. Six1 gene overexpression has been strongly associated with aggressiveness, invasiveness, and poor prognosis of different cancers. In this study, we investigated the role of Six1 signaling in resistance of MCF-7 breast cancer cells to taxanes. We first established in vitro paclitaxel-resistant MCF-7 breast cancer cells. Morphological modifications in paclitaxel-resistant cells were examined via light microscopic images and fluorescence-activated cell sorting analysis. Applying quantitative real-time polymerase chain reaction, we measured Six1, B-cell lymphoma/leukemia(BCL-2), BAX, and P53 mRNA expression levels in both non-resistant and resistant cells. Resistant cells were developed from the parent MCF-7 cells by applying increasing concentrations of paclitaxel up to 64 nM. The inhibitory concentration 50% value in resistant cells increased from 3.5 ± 0.03 to 511 ± 10.22 nM (p = 0.015). In paclitaxel-resistant cells, there was a significant increase in Six1 and BCL-2 mRNA levels (p = 0.0007) with a marked decrease in pro-apoptotic Bax mRNA expression level (p = 0.03); however, there was no significant change in P53 expression (p = 0.025). Our results suggest that identifying cancer patients with high Six1 expression and then inhibition of Six1 signaling can improve the efficiency of chemotherapeutic agents in the induction of apoptosis.

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Author Biography

Nasser Samadi, Drug Applied Research Center, Faculty of Medicine, Tabriz University of Medical Sciences
    

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Published
2016-01-01
How to Cite
1.
Armat M, Oghabi Bakhshaiesh T, Sabzichi M, Shanehbandi D, Sharifi S, Molavi O, Mohammadian J, Saeid Hejazi M, Samadi N. The role of Six1 signaling in paclitaxel-dependent apoptosis in MCF-7 cell line. Bosn J of Basic Med Sci [Internet]. 2016Jan.1 [cited 2019Nov.13];16(1):28-4. Available from: https://bjbms.org/ojs/index.php/bjbms/article/view/674
Section
Pathology