Department of Biological Models, Institute of Biochemistry, Life Sciences Center, Vilnius University, 10257 Vilnius, Lithuania.
Int J Mol Sci. 2023 Jun 15;24(12):10192. doi: 10.3390/ijms241210192.
Resistance to the chemotherapeutic agents in the clinical management of cancer remains a significant challenge, and the mechanical environment of cancer cells is one of the major determinants of this. Stiffening of the environment is usually associated with increased chemoresistance of cancer cells, although this process depends on the type of cancer. Breast cancer is the most frequently diagnosed cancer, and more than half a million people die from it each year worldwide. In this study, we used the most frequent (70% of diagnosed cases) breast cancer phenotype, representing the MCF-7 cell line, to investigate the influence of surface stiffness on its sensitivity to one of the most commonly used anticancer drugs-doxorubicin. We showed that the mechanical environment affected MCF-7 proliferation, adhesion, and the expression and activation of mitogen-activated protein kinases (MAPKs). Furthermore, the role of MAPKs in response to doxorubicin was dependent on surface stiffness; nevertheless, surface stiffness did not affect MCF-7 resistance to doxorubicin.
在癌症的临床治疗中,对化疗药物的耐药性仍然是一个重大挑战,而癌细胞的机械环境是其中的主要决定因素之一。通常情况下,环境的变硬与癌细胞的化疗耐药性增加有关,尽管这一过程取决于癌症的类型。乳腺癌是最常见的癌症类型,全世界每年有超过 50 万人因此而死亡。在这项研究中,我们使用了最常见的(70%的诊断病例)乳腺癌表型,即 MCF-7 细胞系,来研究表面硬度对其对最常用的抗癌药物之一——多柔比星的敏感性的影响。我们发现,机械环境会影响 MCF-7 的增殖、黏附以及丝裂原活化蛋白激酶(MAPKs)的表达和激活。此外,MAPKs 在多柔比星反应中的作用依赖于表面硬度;然而,表面硬度并不影响 MCF-7 对多柔比星的耐药性。