Paclitaxel-based chemotherapy is a common strategy to treat patients with triple-negative breast cancer (TNBC). As paclitaxel resistance is still a clinical issue in treating TNBCs, identifying molecular markers for predicting pathologic responses to paclitaxel treatment is thus urgently needed. Here, we report that an AT-rich interaction domain 1A (ARID1A) transcript is up-regulated in paclitaxel-sensitive TNBC cells but down-regulated in paclitaxel-resistant cells upon paclitaxel treatment. Moreover, ARID1A expression was negatively correlated with the IC50 concentration of paclitaxel in the tested TNBC cell lines. Kaplan-Meier analyses revealed that ARID1A down-regulation was related to a poorer response to paclitaxel-based chemotherapy in patients with TNBCs as measured by the recurrence-free survival probability. The pharmaceutical inhibition with p38MAPK-specific inhibitor SCIO-469 revealed that p38MAPK-related signalling axis regulates ARID1A expression and thereby modulates paclitaxel sensitivity in TNBC cells. These findings suggest that ARID1A could be used as a prognostic factor to estimate the pathological complete response for TNBC patients who decide to receive paclitaxel-based chemotherapy.
Keywords: ARID1A; chemotherapy; p38MAPK; paclitaxel; triple-negative breast cancer.
© 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.