The nanotension relief agent was demonstrated to inhibit the synthesis of phosphorylated myosin light chain by blocking the Rho/Rho-associated serine/threonine kinase (ROCK) pathway, triggering the swift transformation of high-tension CAFs into low-tension CAFs in PDAC tissue, which relieves TSS and enhances drug penetration in Panc02/NIH-3T3 multicellular tumor spheroids. This evidence concerns the gene RHO and neoplasm.