Apoptosis-related BCL2-family Members: Key Players in Chemotherapy
Apoptosis-related BCL2-family Members: Key Players in Chemotherapy
复制标题
DOI：
10.2174/18715206113139990091
复制
发表时间：
2014-03-01
影响因子：
2.8
通讯作者：
Scorilas, Andreas
中科院分区：
文献类型：
--
作者：
Kontos, Christos K.;Christodoulou, Maria-Ioanna;Scorilas, Andreas
经典化疗药物如有丝分裂抑制剂（纺锤体毒物）、烷化剂、抗代谢物、拓扑异构酶抑制剂和蒽二酮（蒽环类药物）抑制DNA合成和有丝分裂，从而杀死或阻碍快速分裂细胞的增殖。在过去的十年中，靶向治疗比传统治疗方案具有优势，因为它对癌症更有效，而且对正常细胞的危害也小得多，从而最大限度地减少化疗的副作用。这种类型的治疗通过抑制肿瘤生长和转移所需的特定靶分子的功能来阻止癌细胞的增殖。靶向治疗剂包括单克隆抗体和小分子抑制剂，它们最常见地靶向受体和/或非受体酪氨酸激酶。 BCL2 凋亡相关家族的大多数成员调节细胞命运作为对抗肿瘤药物的反应。这些基因的 mRNA 和蛋白质水平的调节通常与各种类型的癌细胞对化疗药物的敏感性或耐药性相关。此外，抗癌药物治疗诱导的 BCL2 家族成员表达的改变可以触发或简单地促进细胞凋亡。在这篇综述中，我们总结了抗肿瘤药物直接或间接引起的凋亡相关基因表达变化的信息，以及BCL2家族成员对癌细胞化疗敏感性或化疗耐药性影响的信息。
Classical chemotherapeutic agents such as mitotic inhibitors (spindle poisons), alkylating agents, antimetabolites, topoisomerase inhibitors, and anthracenediones (anthracyclines) inhibit DNA synthesis and mitosis, thereby killing or impeding the proliferation of rapidly dividing cells. During the last decade, targeted therapy has gained advantage over conventional treatment regimens, as it is more effective against cancer and also much less harmful to normal cells, thus minimizing the side-effects of chemotherapy. This type of treatment blocks the proliferation of cancer cells by inhibiting the function of specific targeted molecules needed for tumor growth and metastasis. Targeted therapy agents include monoclonal antibodies and small-molecule inhibitors, which most commonly target receptor and/or non-receptor tyrosine kinases. Most members of the BCL2 apoptosis-related family regulate cellular fate as a response to antineoplastic agents. Modulations at the mRNA and protein levels of these genes are usually associated with sensitivity or resistance of various types of cancer cells to chemotherapeutic drugs. Moreover, alterations in expression of BCL2-family members, induced by anticancer drug treatment, can trigger or simply facilitate apoptosis. In this review, we summarize information about changes in apoptosis-related gene expression caused directly or indirectly by antineoplastic agents, as well as about the impact of BCL2-family members on the chemosensitivity or chemoresistance of cancer cells.