The neuropeptide substance P promotes breast cancer cell growth through the NK1 receptor, and both genetic silencing and the NK1R antagonist aprepitant suppressed tumor proliferation and induced cell death in vitro and in vivo.
Aprepitant suppressed breast cancerThe FDA-approved NK1R antagonist aprepitant inhibited breast cancer cell proliferation and induced apoptosis, matching the effects of genetic NK1R silencing — suggesting a repurposing opportunity
What the researchers found
The study established a direct regulatory link between miR-34b/c-5p and NK1R in breast cancer. Key findings across multiple approaches:
- miR-34b/c-5p and truncated NK1R expression in 50 breast cancer patients correlated with tumor stage and Ki67 (proliferation marker)
- Overexpressing miR-34b/c-5p or silencing NK1R suppressed proliferation, induced G2/M arrest, and triggered apoptosis in MDA-MB-231 and MCF-7 breast cancer cells
- The NK1R antagonist aprepitant produced similar anti-cancer effects
- Substance P (the endogenous NK1R agonist) rescued cell growth when miR-34b/c-5p was overexpressed or NK1R was silenced, confirming pathway specificity
- In vivo xenograft models confirmed that miR-34b/c-5p overexpression or NK1R silencing reduced tumorigenicity
Why it matters
Aprepitant is already an FDA-approved drug (used for chemotherapy-induced nausea), and this study provides mechanistic evidence that it could be repurposed for breast cancer treatment. The substance P/NK1R pathway is increasingly recognized as a cancer driver across multiple tumor types, and this study provides both the molecular mechanism (via miR-34b/c-5p regulation) and clinical correlation data to support therapeutic targeting.
How the study worked
The researchers used multiple breast cancer cell lines (MDA-MB-231, MCF-7, T47D, SK-BR-3) and HEK-293T cells. NK1R regulation by miR-34 was confirmed by Western blot, qRT-PCR, and luciferase assays. Clinical correlation was assessed in 50 breast cancer patient samples. Cell proliferation was measured by CCK-8 and colony formation assays; apoptosis and cell cycle by flow cytometry. Cells were transfected with miR-34b/c-5p mimics or NK1R-siRNA, with or without substance P treatment or aprepitant. In vivo validation used BALB/c nude mouse xenograft models.
What this study cannot tell us
The clinical correlation was based on only 50 patient samples, which limits statistical power. The in vivo studies used immunocompromised nude mice with xenograft tumors, which don't replicate human immune responses to cancer. Aprepitant's anti-cancer doses may differ from its approved anti-nausea doses, and therapeutic window in breast cancer patients is unknown. The study did not assess whether aprepitant interferes with standard breast cancer chemotherapy.
How to read the evidence
This is a comprehensive preclinical study combining patient tissue analysis, multiple cell line experiments, pharmacological validation, and in vivo mouse models. The multi-layered approach is a strength, but clinical evidence for NK1R-targeted breast cancer therapy is not yet available.
When this study was published
Published in 2019, this study contributed to growing interest in the substance P/NK1R pathway as a cancer target. The concept of repurposing aprepitant for oncology continues to be explored.
The bigger picture
The substance P/NK1R axis has been implicated in multiple cancers beyond breast (pancreatic, colorectal, glioma), making this a broadly relevant finding. This study adds a new layer by connecting NK1R to the miR-34 tumor suppressor pathway — one of the most studied microRNA families in cancer. The ability to block this pathway with aprepitant, an existing drug, accelerates the translational timeline compared to developing new therapeutics from scratch.
Questions still open
- Could aprepitant be tested as an adjuvant therapy alongside standard breast cancer chemotherapy in clinical trials?
- Does the substance P/NK1R pathway play a similar tumor-promoting role in all breast cancer subtypes or mainly in specific molecular subtypes?
- Are patients with higher NK1R expression more likely to respond to NK1R antagonist therapy?
Common questions
What is substance P and how does it promote cancer?
Could aprepitant become a breast cancer treatment?
Read the original research
MiR-34b/c-5p and the neurokinin-1 receptor regulate breast cancer cell proliferation and apoptosis.
Cell proliferation, 52(1), e12527
Citation
Zhang, Lufang; Wang, Lushan; Dong, Dong; Wang, Zhiyong; Ji, Wei; Yu, Man; Zhang, Fei; Niu, Ruifang; Zhou, Yunli. (2019). MiR-34b/c-5p and the neurokinin-1 receptor regulate breast cancer cell proliferation and apoptosis.. Cell proliferation, 52(1), e12527. https://doi.org/10.1111/cpr.12527