Inhibition of NLRP3 inflammasome contributes to paclitaxel efficacy in triple negative breast cancer treatment

Abstract

Abstract Chronic inflammation and NLRP3 inflammasome activation are among the determining factors of breast malignancies. Paclitaxel (PTX) is a drug used in breast cancer treatment which sustains prolonged inflammation, reducing the effectiveness of chemotherapy. Considering the impact of inflammatory processes in cancer progression, there is a strong concern to develop therapeutic strategy targeting NLRP3 inflammasome for triple-negative breast cancer (TNBC) treatment. Therefore, the aim of this study was to evaluate the potential of PTX and NLRP3 inflammasome modulation to counterbalance TNBC by inducing programmed cell death and inhibiting the activity of pro-inflammatory cytokines. The obtained results suggested the strong interaction between NLRP3 inflammasome and TNBC and revealed that pharmacological inhibition, using NLRP3-specific inhibitor MCC950, and genetic silencing of NLRP3 inflammasome using specific small interfering RNA, reduced inflammatory responses and facilitated PTX-determined tumor cell death. Thus, NLRP3 inflammasome manipulation in combination with anti-tumor drugs opens up new therapeutic perspectives for TNBC therapy.

Keywords

• TNBC
• NLRP3 inflammasome
• Paclitaxel
• MCC950
• siRNA