Baritaki Stavroula, Apostolakis Stavros, Kanellou Peggy, Dimanche-Boitrel Marie-Therese, Spandidos Demetrios A, Bonavida Benjamin
Department of Microbiology, Immunology, and Molecular Genetics, Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA, University of California, Los Angeles, California 90095, USA.
Adv Cancer Res. 2007;98:149-90. doi: 10.1016/S0065-230X(06)98005-1.
In recent years, significant development and improvement have been observed in the treatment of cancer; however, relapses and recurrences occur frequently and there have not been any current therapies to treat such cancers. Cancers resistant to conventional therapies develop several mechanisms to escape death-inducing stimuli. A poorly understood mechanism is the involvement of the cancer cell plasma membrane composition and architecture and their involvement in regulating drug-inducing stimuli leading to cell death. Although the basic structure of the biological membrane was established 80 years ago, study of the physical properties of lipid bilayers still provides significant information regarding membrane organization and dynamics. Membrane fluidity is probably the most important physicochemical property of cell membranes. Alterations of membrane fluidity can seriously affect functional properties of the cell and induction of apoptotic pathways resulting in cell death. The role of membrane fluidity in the apoptotic process is clearly exemplified as it is seriously disrupted as a result of cell injury. The molecular signaling pathways leading to apoptosis are currently promising areas of research investigation and lead to unravel the underlying molecular mechanisms of tumor cells resistance to apoptotic stimuli and hence the development of new effective therapeutic agents. Recent findings indicate that most anticancer agents induce apoptosis, directly or indirectly, through alterations of tumor cell membrane fluidity. The present chapter summarizes the relationship between alterations of tumor cell membrane fluidity and tumor cell response to apoptotic-inducing stimuli. Several potential therapeutic applications directed at tumor cell membrane fluidity are proposed.
近年来，癌症治疗取得了显著进展和改善；然而，复发和再发情况频繁发生，目前尚无治疗此类癌症的疗法。对传统疗法耐药的癌症会产生多种机制以逃避诱导死亡的刺激。一种尚未完全理解的机制是癌细胞质膜的组成和结构及其在调节导致细胞死亡的药物诱导刺激中的作用。尽管生物膜的基本结构在80年前就已确立，但对脂质双层物理性质的研究仍能提供有关膜组织和动力学的重要信息。膜流动性可能是细胞膜最重要的物理化学性质。膜流动性的改变会严重影响细胞的功能特性并诱导导致细胞死亡的凋亡途径。膜流动性在凋亡过程中的作用在细胞损伤导致其严重破坏时得到了明显体现。导致凋亡的分子信号通路是目前有前景的研究领域，有助于揭示肿瘤细胞对凋亡刺激耐药的潜在分子机制，从而开发新的有效治疗药物。最近的研究结果表明，大多数抗癌药物通过改变肿瘤细胞膜流动性直接或间接诱导凋亡。本章总结了肿瘤细胞膜流动性改变与肿瘤细胞对凋亡诱导刺激反应之间的关系。提出了几种针对肿瘤细胞膜流动性的潜在治疗应用。
