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Low doses of Paclitaxel repress breast cancer invasion through DJ ‐1/ KLF 17 signalling pathway
Author(s) -
Ismail Ismail Ahmed,
ElSokkary Gamal H,
Saber Saber H
Publication year - 2018
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/1440-1681.12960
Subject(s) - paclitaxel , breast cancer , metastasis , cancer research , cancer , cytotoxicity , chemotherapy , medicine , biology , in vitro , biochemistry
Summary Paclitaxel (taxol) is an important agent against many tumours, including breast cancer. Ample data documents that paclitaxel inhibits breast cancer metastasis while others prove that paclitaxel enhances breast cancer metastasis. The mechanisms by which paclitaxel exerts its action are not well established. This study focuses on the effect of paclitaxel, particularly the low doses on breast cancer metastasis and the mechanisms that regulate it. Current results show that, paclitaxel exerts significant cytotoxicity even at low doses in both MCF ‐7 and MDA ‐ MB ‐231 cells. Interestingly, paclitaxel significantly inhibits cell invasion and migration, decreases Snail and increases E‐cadherin mRNA expression levels at the indicated low doses. Furthermore, paclitaxel‐inhibiting breast cancer metastasis is associated with down‐regulation of DJ ‐1 and ID ‐1 mRNA expression level with a concurrent increase in KLF 17 expression. Under the same experimental conditions, paclitaxel induces KLF 17 and concurrently represses ID ‐1 protein levels. Our results show for the first time that paclitaxel inhibits breast cancer metastasis through regulating DJ ‐1/ KLF 17/ ID ‐1 signalling pathway; repressed DJ ‐1 and ID ‐1 and enhanced KLF 17 expression.