Ivermectin and Metformin Combination Promotes Autophagy in Breast Cancer via PI3K/AKT/mTOR Pathway
Chinese researchers found that combining ivermectin with metformin significantly inhibited MCF-7 breast cancer cell viability, migration, and invasion by suppressing PI3K/AKT/mTOR signaling and triggering autophagy.
By Sanare Lab · August 6, 2026 · 5 min read
Key Takeaway
A July 2026 study published in Oncology Reports found that combining ivermectin (IVM) — an antiparasitic drug — with metformin (MET) — a widely used diabetes medication — significantly inhibited MCF-7 breast cancer cell viability, migration, and invasiveness. The combination suppressed the PI3K/AKT/mTOR signaling pathway (a key cancer survival pathway), promoted autophagy (a cellular self-digestion process that can kill cancer cells), and elevated reactive oxygen species (ROS) — markers of oxidative stress — more than either drug alone. This is preclinical cell-culture research; neither drug is approved for breast cancer treatment in this combination.
Drug repurposing — finding new uses for existing medications — is an increasingly attractive strategy in oncology. Two drugs with established safety profiles, ivermectin (an antiparasitic) and metformin (a first-line diabetes medication), have each shown individual anticancer activity in preclinical studies. A 2026 study investigated whether combining them could produce synergistic effects against breast cancer.
Published in July 2026 in Oncology Reports by Feng H, He L, Umar T, and colleagues from Henan Vocational College of Agriculture and Huazhong Agricultural University (China), the study examined the combined effects of ivermectin and metformin on MCF-7 human breast cancer cells — one of the most widely studied ER-positive breast cancer cell lines.
Table of Contents
- Study Design and Methods
- Key Findings
- The PI3K/AKT/mTOR Pathway Explained
- Limitations and Context
- Frequently Asked Questions
- Shop Sanare Lab
- References
Study Design and Methods
The researchers used MCF-7 human breast cancer cells and assessed the effects of ivermectin alone, metformin alone, and the combination. The following methods were employed:
- Cell Counting Kit-8 (CCK-8) assay: To measure cell viability and proliferation
- Transwell migration and scratch assays: To assess invasive and migratory capabilities
- Transcriptomic analysis: To identify differentially expressed genes and key signaling pathways
- Flow cytometry: To quantify reactive oxygen species (ROS) levels
- Transmission electron microscopy: To visualize autophagosome formation (structures that indicate autophagy)
- Western blotting and immunofluorescence: To detect changes in key protein expression
Key Findings
| Outcome Measured | Result with IVM + MET Combination |
|---|---|
| Cell viability (proliferation) | Significantly inhibited after 24 h; concentration-dependent reduction |
| Cell migration and invasion | Significantly reduced (Transwell and scratch assays) |
| PI3K/AKT/mTOR pathway | Reduced phosphorylation of p-PI3K, p-AKT, and p-mTOR |
| THBS1 (thrombospondin-1) | Decreased expression; validated as positive regulator of PI3K/AKT/mTOR |
| Reactive oxygen species (ROS) | Significantly elevated vs. single-drug groups (oxidative stress induction) |
| Autophagy | Autophagosome formation confirmed by transmission electron microscopy |
Transcriptomic analysis identified significant enrichment of the PI3K/AKT/mTOR signaling pathway as the primary mechanism. The study also identified THBS1 (thrombospondin-1) as a mediator: THBS1 overexpression plasmid experiments confirmed that THBS1 positively regulates PI3K/AKT/mTOR phosphorylation, and the combination therapy reduced THBS1 expression, thereby suppressing the pathway.
The PI3K/AKT/mTOR Pathway Explained
The PI3K/AKT/mTOR signaling pathway is one of the most frequently activated pathways in human cancers. It controls cell growth, survival, metabolism, and protein synthesis. When this pathway is overactive — as it often is in breast cancer — cancer cells grow and survive even under conditions that would normally trigger cell death.
Phosphorylated (activated) forms of PI3K (phosphoinositide 3-kinase), AKT (protein kinase B), and mTOR (mechanistic target of rapamycin) are markers of pathway activation. By reducing the phosphorylation of all three proteins, the ivermectin-metformin combination effectively "turns down" this pro-survival signaling cascade.
Autophagy — the cellular process of self-digestion — can serve as a cancer-killing mechanism when induced at high levels. The combination's ability to promote autophagosome formation (confirmed by electron microscopy) suggests it triggers this process in MCF-7 cells.
Limitations and Context
This study used a single breast cancer cell line (MCF-7), which limits generalizability. The research is in vitro only — no animal models or human data are presented. The concentrations of ivermectin and metformin used in cell culture experiments may not be achievable at tumor sites in humans at standard doses. Metformin is approved for type 2 diabetes, not cancer; ivermectin is approved for antiparasitic indications only. Neither drug should be used for cancer treatment outside of a supervised clinical trial.
For background, see our guide to how ivermectin works.
We cover this in more depth in our article on ivermectin cancer protocols and dosing.
For the fuller picture, read our deep dive into ivermectin and cancer immunotherapy.
Plan the numbers in our interactive dosing workspace.
For background, see our guide to the ivermectin immunotherapy trial (NCT05318469).
Frequently Asked Questions
What is the PI3K/AKT/mTOR pathway and why does it matter in cancer?
The PI3K/AKT/mTOR pathway is a major signaling cascade that controls cell growth, survival, and metabolism. In many cancers — including breast cancer — this pathway is overactivated, helping cancer cells grow and survive. Drugs that suppress this pathway (like the combination studied here) can potentially slow cancer cell growth and trigger cell death. Several approved cancer drugs already target components of this pathway.
What is autophagy and how can it kill cancer cells?
Autophagy is a cellular process in which cells break down and recycle their own components — essentially a form of self-digestion. At low levels, autophagy helps cells survive stress. At high levels, it can trigger cell death. The study confirmed autophagy induction in MCF-7 cells treated with the ivermectin-metformin combination by visualizing autophagosome formation (the structures that carry cellular material for digestion) using electron microscopy.
Why was metformin chosen as a combination partner for ivermectin?
Metformin is a widely used, well-tolerated diabetes drug that has shown anticancer properties in multiple preclinical studies, partly through its ability to inhibit the PI3K/AKT/mTOR pathway and reduce cellular energy availability. Combining it with ivermectin — which has its own anticancer mechanisms — was hypothesized to produce synergistic effects. The study found that the combination elevated reactive oxygen species (ROS) more than either drug alone, suggesting additive or synergistic oxidative stress induction.
Should breast cancer patients take ivermectin and metformin together?
No. This is preclinical cell-culture research. Neither ivermectin nor metformin is approved for breast cancer treatment. The concentrations used in laboratory studies may not be achievable safely in humans. Patients should not self-administer these drugs for cancer treatment. Any interest in investigational approaches should be discussed with a qualified oncologist, ideally within the context of a clinical trial.
Chinese scientists combined two repurposed drugs — ivermectin (an antiparasitic) and metformin (a diabetes medication) — and tested them on breast cancer cells. The combination was more effective than either drug alone at stopping cancer cells from growing and spreading. It worked by switching off a key cancer survival pathway (PI3K/AKT/mTOR — a signaling chain that helps cancer cells grow) and triggering autophagy (a process where cells essentially digest themselves). The combination also produced more oxidative stress (cellular damage from reactive oxygen species) than either drug alone. This is early-stage laboratory research; neither drug is approved for breast cancer and this combination has not been tested in human patients.
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References
1. Feng H, He L, Umar T, Wang H, Gao Y, Chen G, Sun P, Yin L, Zhao W, Lu H, Deng G, Qiu C. Combination of ivermectin and metformin promotes autophagy in MCF-7 cells by inhibiting phosphorylation of the PI3K/AKT/mTOR pathway. Oncol Rep. 2026 Jul;56(1):131. doi: 10.3892/or.2026.9136. Epub 2026 May 15. PubMed PMID: 42138203
Medical Disclaimer
This article is for educational and informational purposes only. It is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.
Sanare Lab
Science-based health education team reviewing published research on repurposed drugs, integrative oncology, and evidence-based protocols.