Low-intensity vibration (LIV) cellular mechanotherapy reprograms tumor transcriptomes to suppress cancer-promoting inflammation

SUMMARY LIV is a non-pharmacological intervention for multiple pathologies, most notably pain, yet its potential in oncology remains unexplored due to poorly understood mechanotransduction pathways. Its therapeutic efficacy depends on precise dosing parameters - frequency, amplitude, and duration; suboptimal application, whether excessive or insufficient, risks exacerbating symptoms or rendering treatment ineffective. In a breast cancer–immune cell co-culture model, a 15-min regimen of 90-Hz, 0.43-g LIV attenuates protumorigenic crosstalk by suppressing proinflammatory cytokines and reprogramming malignant cells into a transient metastasis-incompetent “benignant” state that retains oncogenic markers but loses invasive capacity. Our results reveal LIV as a non-drug inhibitor of IFNγ and CXCL12β - silencing IFNγ impairs inflammatory bursts, while silencing CXCL12β starves the CXCR4/CXCR7 axis, depriving tumor cells of motility cues. LIV enforces a genome-wide transcriptional brake, upregulating tumor-suppressive miRNAs (hsa-miR-141, hsa-miR-122) while downregulating protumorigenic miRNAs (hsa-miR-105-5p, hsa-miR-181a-5p). This work repositions LIV as a non-drug modality for coordinately targeting multiple cancer hallmarks. Graphical abstract Highlights Dosing Precision LIV mechanotherapy has an optimal therapeutic window. Too little is ineffective, while too much can exacerbate symptoms. This mirrors the pharmacokinetic language of classical pharmacology. The “Benignant” Concept A 15-min regimen of 90-Hz, 0.43-g LIV attenuates protumorigenic crosstalk by suppressing proinflammatory cytokines and reprogramming malignant cells into a transient, metastasis-incompetent benignant state defined by mechanical constraint rather than pharmacological intervention. Dual Cytokine Silencing LIV acts as a non-pharmaco-logical inhibitor of IFNγ and CXCL12β. IFNγ is a double-edged sword in cancer (pro-immunity vs. exhaustion), and CXCL12β is the specific isoform implicated in metastasis. Targeting both simultaneously addresses immune crosstalk and chemotaxis. In brief Meena et al. demonstrate that the efficacy of LIV hinges on optimal dosing parameters. When applied correctly, it functions as a non-drug modality to target multiple oncogenic and inflammatory pathways. At the molecular level, LIV drives global transcriptional repression via miRNA regulation, increasing tumor-suppressive miRNAs (hsa-miR-141, hsa-miR-122) and decreasing protumorigenic miRNAs (hsa-miR-105-5p, hsa-miR-181a-5p).