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Extracellular Matrix Proteins Modulate Antimigratory and Apoptotic Effects of Doxorubicin

机译:细胞外基质蛋白调节阿霉素的抗迁移和凋亡作用

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Anticancer drug resistance is a multifactorial process that includes acquired andde novodrug resistances. Acquired resistance develops during treatment, whilede novoresistance is the primary way for tumor cells to escape chemotherapy. Tumor microenvironment has been recently shown to be one of the important factors contributing tode novoresistance and called environment-mediated drug resistance (EMDR). Two forms of EMDR have been described: soluble factor-mediated drug resistance (SFM-DR) and cell adhesion-mediated drug resistance (CAM-DR). Anthracyclines, among the most potent chemotherapeutic agents, are widely used in clinics against hematopoietic and solid tumors. Their main mechanism of action relies on the inhibition of topoisomerase I and/or II and the induction of apoptosis. Beyond this well-known antitumor activity, it has been recently demonstrated that anthracyclines may display potent anti-invasive effects when used at subtoxic concentrations. In this paper, we will describe two particular modes of EMDR by which microenvironment may influence tumor-cell response to one of these anthracyclines, doxorubicin. The first one considers the influence of type I collagen on the antimigratory effect of doxorubicin (CAM-DR). The second considers the protection of tumor cells by thrombospondin-I against doxorubicin-induced apoptosis (SFM-DR).
机译:抗癌药耐药性是一个多因素过程,包括获得性耐药和新药耐药性。在治疗过程中会产生获得性耐药,而抗肿瘤性是肿瘤细胞逃避化疗的主要途径。肿瘤微环境近来已被证明是促成滋味的重要因素之一,被称为环境介导的耐药性(EMDR)。已经描述了两种形式的EMDR:可溶性因子介导的耐药性(SFM-DR)和细胞粘附介导的耐药性(CAM-DR)。蒽环类药物是最有效的化疗药物之一,在临床上广泛用于抗造血和实体瘤。它们的主要作用机理依赖于拓扑异构酶I和/或II的抑制以及细胞凋亡的诱导。除了这种众所周知的抗肿瘤活性外,最近还证明了蒽环类药物在亚毒性浓度下使用时可能会显示出强大的抗侵袭作用。在本文中,我们将描述两种特定的EMDR模式,微环境可能通过这些模式影响肿瘤细胞对其中一种蒽环类药物阿霉素的反应。第一个考虑了I型胶原蛋白对阿霉素(CAM-DR)的抗迁移作用的影响。第二个考虑了血小板反应蛋白-I对阿霉素诱导的细胞凋亡(SFM-DR)的保护。

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