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Increasing evidence shows that matrix stiffness plays a critical role in affecting the phenotype and behavior of tumor cells. We report that matrix stiffness significantly regulated the proliferation and chemotherapeutic response of Hep-2 cells. Increasing substrate stiffness promotes the proliferation of Hep-2 cells. When cultured on soft gels, Hep-2 cells expressed higher level of stem cell markers. Following treatment with cisplatin or 5-FU, we observed reduced apoptosis in Hep-2 cells cultured on soft supports. Sox2 is essential for the chemoresistance of Hep-2 cells cultured in soft stiffness. Our results demonstrated that Sox2 promotes chemoresistance of Hep-2 cells in soft stiffness via upregulating the expression of ABCG2. Our findings will provide a new platform for the future design of anticancer drugs based on the biophysical properties of the tumor site.

Matrix stiffness regulates the proliferation, stemness and chemoresistance of laryngeal squamous cancer cells