Abstract
The use of aspirin has been associated with reduced breast cancer risk, but it is litter known if aspirin overcomes chemoresistance in triple-negative breast cancer (TNBC). Herein, we demonstrated that changes in the expression of Yes-associated protein (YAP) and β-catenin might be a promising predictive biomarker for neoadjuvant chemotherapy sensitivity in TNBC patients. Inhibition of YAP or β-catenin enhanced the cytotoxicity of the anti-microtubule agents docetaxel and vinorelbine against drug-resistant TNBC cells as well as the sensitivity of these cells to the agents in vitro and in vivo. Interestingly, aspirin not only significantly inhibited the growth of TNBC cells, but also attenuated YAP and β-catenin expression by upregulating the E3 ubiquitin ligase β-TrCP to abolished docetaxel and vinorelbine resistance. The combination of aspirin and docetaxel or vinorelbine remarkably inhibited the growth of drug-resistant TNBC cells in vitro and in vivo. Moreover, TNBC patients with high YAP and/or β-catenin expression had a higher risk of relapse or mortality than patients with low YAP and/or β-catenin expression. Collectively, our study discovered a novel role of aspirin based on its anticancer effect, and put forward some possible mechanisms of chemoresistance in TNBC. The combined use of aspirin and anti-microtubule drugs presented several promising therapeutic approaches for TNBC treatment.
Highlights
Breast cancer had one of the highest incidences and one of the highest mortality rates of cancers that affect females in 20181
To explore the roles of Yes-associated protein (YAP) and β-catenin in the carcinogenesis of human breast cancer, we investigated the expression of YAP and β-catenin by IHC in 30 pairs of breast carcinoma and adjacent normal breast tissue specimens
There was no significant difference in YAP expression between the cancer specimens and the adjacent normal tissues (P = 0.081), while β-catenin expression was higher in cancer tissues than in the paired adjacent normal tissues (P < 0.001)
Summary
Breast cancer had one of the highest incidences and one of the highest mortality rates of cancers that affect females in 20181. Despite many advances in targeted molecular therapy, the mortality rate of breast cancer remains very high. Due to the lack of effective therapeutic targets, TNBC is associated with more aggressive behaviours, earlier relapse and poorer prognosis. Docetaxel- and vinorelbine-based regimens have proven to be greatly effective in early and advanced TNBC, respectively[3]. More effective therapeutic strategies for TNBC are urgently needed. Many epidemiological studies have found that tumour mortality decreases exponentially with an increase in aspirin intake in several cancers, including colon, breast, lung, and prostate cancers and cancers of other organs[4,5,6]
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