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

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.