Ivermectin, a novel antiparasitic, has recently emerged as a candidate with unexpected anti-cancer properties. Some studies report that ivermectin suppresses tumor cell proliferation and migration by regulating signaling pathways linked to cytoskeletal remodeling and disease progression. Lung adenocarcinoma, represented by the A549 cell line, remains difficult to treat due to its capacity for invasion, therapeutic resistance, and poor long-term outcomes. This project investigates whether ivermectin can reduce A549 cell migration through modulation of α-SMA associated contractility and related pathway activity. The proposed methodology includes scratch assays to quantify changes in motility following treatment, and molecular analyses to evaluate shifts in expression of migration-linked markers. These findings aim to clarify ivermectin’s mechanistic impact on lung cancer cell movement and offer insight into its potential relevance as a repurposed therapeutic strategy for limiting tumor progression.

My name is Alaika Sridhar, and today I’m going to be talking about my project exploring the effect of ivermectin on A549 lung adenocarcinoma cells.

For context, A549 cells are a non–small cell lung cancer line, a clinically significant cancer type known for its aggressive behavior, high metastatic potential, and resistance to conventional therapies. Because of these challenges, identifying affordable and accessible agents that can reduce cell migration or proliferation is extremely important.

Although ivermectin is well-known as an antiparasitic drug, emerging studies show that it can inhibit proliferation across several tumor types by regulating key signaling pathways. This has generated growing interest in repurposing ivermectin as an anticancer agent.
However, its effects on A549 cells, particularly through cytoskeletal and migration-related pathways, are still not well understood. That gap is what this project aims to address.

Hypothesis

I hypothesize that ivermectin will inhibit pro-migratory pathways in A549 lung adenocarcinoma cells, specifically through modulation of the TGF-β1 / α-smooth muscle actin signaling pathway, ultimately reducing motility. The primary marker I’ll be examining is α-SMA, which is tied to cell movement and cytoskeletal remodeling.

Methods Overview

Due to delays in obtaining materials, this project was not fully completed during the semester, but the proposed methodology is as follows:

Toxicity Testing
A549 cells will be treated with increasing concentrations of ivermectin to determine a non-lethal dose, one that affects motility without compromising viability. This ensures observed effects reflect pathway regulation rather than cell death.

Scratch Assay
A wound will be introduced into a confluent monolayer of cells, followed by ivermectin treatment. I will measure rate of gap closure to assess whether cell migration is slowed.

qPCR Analysis
Gene expression of α-SMA and other motility-associated markers will be quantified. Reduced expression would suggest suppression of cytoskeletal pathways.

Western Blot
Protein abundance will be assessed to determine whether transcriptional changes translate to functional protein-level alterations.

Data Analysis
Imaging and quantification will be performed using ImageJ, followed by Tukey’s post-hoc statistical testing to determine significance.

Significance and Future Directions

A549 cells represent an aggressive cancer subtype that remains difficult to treat.
If ivermectin reduces their migration, it may offer a promising low-cost avenue to limit metastasis which is one of the leading causes of mortality in lung cancer.

Once I complete the experiment, I plan to:

• explore additional pathway targets,
• investigate time dependent responses, and
• extend findings into in vivo models.

This work contributes to growing interest in drug repurposing, which offers inexpensive and accessible strategies to improve cancer treatment.

Acknowledgments

I’d like to thank the OSCAR Office at George Mason University for funding this research and Dr. Geraldine Grant and everyone in the Grant Lab for their support and guidance.

Thank you.