紫杉醇耐药会增加前列腺癌细胞对其他微环境应激的敏感性。
Resistance to paclitaxel increases the sensitivity to other microenvironmental stresses in prostate cancer cells.
机构信息
Department of Urology, James Buchanan Brady Urological Institute, The Johns Hopkins School of Medicine, Baltimore, Maryland 21287, USA.
出版信息
J Cell Biochem. 2011 Aug;112(8):2125-37. doi: 10.1002/jcb.23134.
The microenvironment is central to many aspects of cancer pathobiology and has been proposed to play a role in the development of cancer cell resistance to therapy. To examine the response to microenvironmental conditions, two paclitaxel resistant prostate cancer (PCa) cell lines (stable and reversible) and one reversible heat resistant cell line were studied. In comparison to their parental cell lines, both paclitaxel resistant cell lines (stable and reversible) were more sensitive to microenvironmental heat, potentially yielding a synergistic therapeutic opportunity. In the two phenotypic cells repopulated after acute heat or paclitaxel treatments, there was an inverse correlation between paclitaxel and heat resistance: resistance to paclitaxel imparted sensitivity to heat; resistance to heat imparted sensitivity to paclitaxel. These studies indicate that as cancer cells evolve resistance to single microenvironmental stress they may be more sensitive to others, perhaps allowing us to design new approaches for PCa therapy.
微环境是癌症病理生物学多方面的核心，据推测其在癌细胞对治疗产生耐药性的过程中发挥了作用。为了研究对微环境条件的反应，我们研究了两种紫杉醇耐药前列腺癌（PCa）细胞系（稳定型和可逆型）和一种可逆型耐热细胞系。与亲本细胞系相比，两种紫杉醇耐药细胞系（稳定型和可逆型）对微环境热更敏感，可能产生协同治疗机会。在急性热或紫杉醇处理后重新增殖的两种表型细胞中，紫杉醇耐药性和耐热性之间存在反比关系：对紫杉醇的耐药性赋予了对热的敏感性；耐热性赋予了对紫杉醇的敏感性。这些研究表明，随着癌细胞对单一微环境压力产生耐药性，它们可能对其他压力更敏感，也许使我们能够为 PCa 治疗设计新方法。
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