Department of Basic Science, Faculty of Veterinary Medicine, University of Tabriz, Tabriz 5166616471, Iran.
Sabanci University Nanotechnology Research and Application Center (SUNUM), Tuzla, Istanbul 34956, Turkey.
Int J Mol Sci. 2020 Jun 3;21(11):4002. doi: 10.3390/ijms21114002.
Therapy resistance is a characteristic of cancer cells that significantly reduces the effectiveness of drugs. Despite the popularity of cisplatin (CP) as a chemotherapeutic agent, which is widely used in the treatment of various types of cancer, resistance of cancer cells to CP chemotherapy has been extensively observed. Among various reported mechanism(s), the epithelial-mesenchymal transition (EMT) process can significantly contribute to chemoresistance by converting the motionless epithelial cells into mobile mesenchymal cells and altering cell-cell adhesion as well as the cellular extracellular matrix, leading to invasion of tumor cells. By analyzing the impact of the different molecular pathways such as microRNAs, long non-coding RNAs, nuclear factor-κB (NF-ĸB), phosphoinositide 3-kinase-related protein kinase (PI3K)/Akt, mammalian target rapamycin (mTOR), and Wnt, which play an important role in resistance exhibited to CP therapy, we first give an introduction about the EMT mechanism and its role in drug resistance. We then focus specifically on the molecular pathways involved in drug resistance and the pharmacological strategies that can be used to mitigate this resistance. Overall, we highlight the various targeted signaling pathways that could be considered in future studies to pave the way for the inhibition of EMT-mediated resistance displayed by tumor cells in response to CP exposure.
耐药性是癌细胞的一个特征，它大大降低了药物的疗效。尽管顺铂（CP）作为一种化疗药物被广泛应用于治疗各种类型的癌症，但癌细胞对 CP 化疗的耐药性已被广泛观察到。在各种报道的机制中，上皮-间充质转化（EMT）过程可通过将静止的上皮细胞转化为运动的间充质细胞，并改变细胞-细胞黏附和细胞外基质，从而导致肿瘤细胞的侵袭，显著促进化疗耐药性。通过分析不同分子途径（如 microRNAs、长非编码 RNA、核因子-κB（NF-ĸB）、磷酸肌醇 3-激酶相关蛋白激酶（PI3K）/Akt、哺乳动物雷帕霉素靶蛋白（mTOR）和 Wnt）的影响，这些分子途径在 CP 治疗耐药性中发挥着重要作用，我们首先介绍了 EMT 机制及其在耐药性中的作用。然后，我们特别关注参与耐药性的分子途径以及可以用来减轻这种耐药性的药理学策略。总的来说，我们强调了各种靶向信号通路，这些信号通路可以在未来的研究中被考虑，为抑制 EMT 介导的肿瘤细胞对 CP 暴露的耐药性铺平道路。
