IRE1α inhibitor enhances paclitaxel sensitivity of triple-negative breast cancer cells
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Updated: Jun 23, 2025
Long-term Live-cell Imaging to Assess Cell Fate in Response to Paclitaxel
Published on: May 14, 2018
1Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, 500 Dong Chuan Rd, Shanghai, 200241, China.
Purpose:
Breast cancer is the most commonly diagnosed cancer in women, and triple-negative breast cancer (TNBC) accounts for approximately 15%-20% of all breast cancers. TNBC is highly invasive and malignant. Due to the lack of relevant receptor markers, the prognosis of TNBC is poor and the five-year survival rate is low. Paclitaxel is the first-line drug for the treatment of TNBC, which can inhibit cell mitosis. However, many patients develop drug resistance during treatment, leading to chemotherapy failure. Therefore, finding new therapeutic combinations to overcome TNBC drug resistance can provide new strategies for improving the survival rate of TNBC patients.
Methods:
Cell viability assay, RT-qPCR, Colony formation assay, Western blot, and Xenogeneic transplantation methods were used to investigate roles and mechanisms of IRE1α/XBP1s pathway in the paclitaxel-resistant TNBC cells, and combined paclitaxel and IRE1α inhibitor in the treatment of TNBC was examined in vitro and in vivo.
Results:
We found activation of UPR in paclitaxel-resistant cells, confirming that IRE1α/XBP1 promotes paclitaxel resistance in TNBC. In addition, we demonstrated that the combination of paclitaxel and IRE1α inhibitors can synergistically inhibit the proliferation of TNBC tumors both in vitro and in vivo,suggesting that IRE1α inhibitors combined with paclitaxel may be a new treatment option for TNBC.
Conclusions:
In this study, we demonstrated the important role of IRE1α signaling in mediating paclitaxel resistance and identified that combination therapies targeting IRE1α signaling could overcome paclitaxel resistance and enhance chemotherapy efficacy.
Insights
Triple-negative breast cancer (TNBC) often becomes resistant to paclitaxel. Combining paclitaxel with IRE1α inhibitors shows promise in overcoming this resistance and improving TNBC treatment outcomes.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Triple-negative breast cancer (TNBC) is an aggressive subtype with poor prognosis.
- Paclitaxel is a first-line treatment, but resistance frequently develops, limiting efficacy.
- Novel therapeutic strategies are needed to overcome paclitaxel resistance in TNBC.
Purpose of the Study:
- To investigate the role of the IRE1α/XBP1s pathway in paclitaxel resistance in TNBC.
- To evaluate the efficacy of combining paclitaxel with IRE1α inhibitors for TNBC treatment.
Main Methods:
- Utilized cell viability assays, RT-qPCR, colony formation assays, and Western blot.
- Examined the IRE1α/XBP1s pathway in paclitaxel-resistant TNBC cells.
- Assessed the combined effect of paclitaxel and IRE1α inhibitors in vitro and in vivo xenograft models.
Main Results:
- Paclitaxel-resistant TNBC cells exhibited activated unfolded protein response (UPR).
- The IRE1α/XBP1s pathway was confirmed to promote paclitaxel resistance in TNBC.
- Combination therapy synergistically inhibited TNBC tumor proliferation both in vitro and in vivo.
Conclusions:
- IRE1α signaling plays a critical role in mediating paclitaxel resistance in TNBC.
- Targeting IRE1α signaling with inhibitors offers a potential strategy to overcome resistance.
- Combination therapy with paclitaxel and IRE1α inhibitors may represent a new treatment option for TNBC.
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