中西医结合预防和逆转癌细胞对抗癌药物的耐药性

Wenzheng Zhang, Xingxing Huang, Bi Chen, Y. Liu, Jiao Feng, Shuiping Liu, Ruonan Zhang, Yu Xiang, Ting Duan, Mingming Zhang, Xia-Yin Chen, Peng Chen, Xinbing Sui, Tian Xie
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摘要

癌症是一种常见而复杂的疾病,具有各种遗传和环境风险。化疗和靶向治疗是治疗晚期癌症患者的主要方法之一。然而,患者长期接受治疗往往会产生耐药现象,使治疗效果大打折扣。因此,开发新的有效治疗策略以克服耐药性是癌症治疗的当务之急。导致耐药性的因素多种多样,包括肿瘤细胞异质性、药物外流、药物失活、肿瘤微环境变化、DNA损伤修复障碍、癌细胞表观遗传学改变等。然而,如何规避耐药性以提高抗癌疗效仍有待确定。目前,克服耐药性最重要的方法是药物联合治疗方案,但容易诱发新的耐药性,甚至多药耐药性(MDR)。而中药 "多成分、多靶点 "的特点,使其成为开发新型辅助治疗药物以逆转耐药性的一个极具吸引力的方向。近年来,已有多种中药化合物被报道可增强抗癌药物的敏感性或克服耐药性,包括榄香烯、布法林、姜黄素、木兰醇、红景天、白藜芦醇、槲皮素等。因此,中医药与传统抗癌药物的结合有望为癌症患者的治疗提供一种增强抗癌效果、克服抗药性的新策略。本文回顾了抗药性的分子机制和治疗策略。我们还讨论了当前中医药克服耐药性的基础研究和临床研究。最后,我们重点讨论了中西医结合作为一种有前途的新治疗方法,在治疗癌症患者时增强抗癌策略的效果或克服抗药性。
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Combination of Chinese and western medicine to prevent and reverse resistance of cancer cells to anticancer drugs
Cancer is a common and complex disease with various genetic and environmental risks. Chemotherapy and targeted therapy are one of the main therapeutic approaches for the treatment of advanced cancer patients. However, prolonged patient treatment often provokes drug resistance phenomena that render the therapeutic treatment highly ineffective. Therefore, the development of novel and effective treatment strategies to overcome drug resistance is urgent for cancer therapy. A variety of factors contribute to drug resistance, including tumor cell heterogeneity, drug efflux, drug inactivation, changes in tumor microenvironment, DNA damage repair disorders, epigenetic alterations in cancer cells and so on. However, how to circumvent drug resistance to improve anticancer efficacy remains to be determined. Currently, the most important approach for overcoming drug resistance is drug combination therapeutic regimen, however, it is easy to induce new drug resistance or even multi-drug resistance (MDR) which is defined as the resistance of cancer cells to multiple anticancer drugs with different structures and mechanisms of action. Whereas, the “multi-components and multi-targets” manifestations of Traditional Chinese Medicine (TCM) make them an attractive direction for developing new adjuvant therapeutics to reverse drug resistance. In recent years, several compounds derived from TCM have been reported to augment sensitivity or overcome resistance of anticancer therapeutic drugs, including elemene, bufalin, curcumin, magnolol, honokiol, resveratrol, quercetin, and so on. Thus, the combination of TCM and conventional anticancer drugs will hopefully provide a novel strategy for enhancing the effects of anticancer strategies and overcoming their resistance in the treatment of cancer patients. In the current paper, we review the molecular mechanisms of drug resistance and the therapeutic strategies. We also discuss the current basic research and clinical studies in overcoming drug resistance from Traditional Chinese Medicine. Finally, we focus the integrated traditional Chinese and Western medicine as a promising new therapeutic approach to enhance the effects of anticancer strategies or overcome their resistance in the treatment of cancer patients.
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