Title | Specific c-Jun N-Terminal Kinase Inhibitor, JNK-IN-8 Suppresses Mesenchymal Profile of PTX-Resistant MCF-7 Cells through Modulating PI3K/Akt, MAPK and Wnt Signaling Pathways |
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Type | Journal article |
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Authors | Ozfiliz Kilbas, P., Sonmez, Ozlem, Uysal Onganer, P., Coker Gurkan, A., Obakan Yerlikaya, P. and Arisan, Elif Damla |
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Abstract | Paclitaxel (PTX) is a widely used chemotherapeutic agent in the treatment of breast cancer, and resistance to PTX is a common failure of breast cancer therapy. Therefore, understanding the effective molecular targets in PTX-resistance gains importance in identifying novel strategies in successful breast cancer therapy approaches. The aim of the study was to investigate the functional role of PTX resistance on MCF-7 cell survival and proliferation related to PI3K/Akt and MAPK pathways. The generated PTX-resistant (PTX-res) MCF-7 cells showed enhanced cell survival, proliferation, and colony formation potential with decreased cell death compared to wt MCF-7 cells. PTX-res MCF-7 cells exhibited increased motility profile with EMT, PI3K/Akt, and MAPK pathway induction. According to the significant SAPK/JNK activation in PTX-res MCF-7 cells, specific c-Jun N-terminal kinase inhibitor, JNK-IN-8 is shown to suppress the migration potential of cells. Treatment of JNK inhibitor suppressed the p38 and SAPK/JNK and Vimentin expression. However, the JNK inhibitor further downregulated Wnt signaling members in PTX-res MCF-7 cells. Therefore, the JNK inhibitor JNK-IN-8 might be used as a potential therapy model to reverse PTX-resistance related to Wnt signaling. |
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Keywords | Paclitaxel |
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| JNK |
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| WNT |
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| drug resistance |
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| breast cancer |
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Journal | Biology |
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Journal citation | 9 (10), p. e320 |
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ISSN | 2079-7737 |
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Year | 2020 |
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Publisher | MDPI |
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Publisher's version | License CC BY 4.0 File Access Level Open (open metadata and files) |
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Digital Object Identifier (DOI) | https://doi.org/10.3390/biology9100320 |
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Publication dates |
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Published | 01 Oct 2020 |
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License | CC BY 4.0 |
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