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非编码 RNA 失调介导肝癌顺铂耐药及治疗策略。

Dysregulation of non-coding RNAs mediates cisplatin resistance in hepatocellular carcinoma and therapeutic strategies.

机构信息

Department of Hemorrhoid and Fistula of Traditional Chinese Medicine, Chaohu Hospital Affiliated to Anhui Medical University, Chaohu, Anhui, 238000, PR China.

Department of Rheumatology and Immunology, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230032, PR China.

出版信息

Pharmacol Res. 2022 Feb;176:105906. doi: 10.1016/j.phrs.2021.105906. Epub 2021 Sep 20.

Abstract

Hepatocellular carcinoma (HCC) is the fourth major contributor to cancer-related deaths worldwide, and patients mostly have poor prognosis. Although several drugs have been approved for the treatment of HCC, cisplatin (CDDP) is still applied in treatment of HCC as a classical chemotherapeutic drug. Unfortunately, the emergence of CDDP resistance has caused HCC patients to exhibit poor drug response. How to mitigate or even reverse CDDP resistance is an urgent clinical issue to be solved. Because of critical roles in biological functional processes and disease developments, non-coding RNAs (ncRNAs) have been extensively studied in HCC in recent years. Importantly, ncRNAs have also been demonstrated to be involved in the development of HCC to CDDP resistance process. Therefore, this review highlighted the regulatory roles of ncRNAs in CDDP resistance of HCC, elucidated the multiple potential mechanisms by which HCC develops CDDP resistance, and attempted to propose multiple drug delivery systems to alleviate CDDP resistance. Recently, ncRNA-based therapy may be a feasible strategy to alleviate CDDP resistance in HCC. Meanwhile, nanoparticles can overcome the deficiencies in ncRNA-based therapy and make it possible to reverse tumor drug resistance. The combined use of these strategies provides clues for reversing CDDP resistance and overcoming the poor prognosis of HCC.

摘要

肝细胞癌 (HCC) 是全球导致癌症相关死亡的第四大主要原因,且患者预后大多较差。尽管已有几种药物被批准用于 HCC 的治疗,但顺铂 (CDDP) 仍作为一种经典的化疗药物应用于 HCC 的治疗中。不幸的是,CDDP 耐药性的出现导致 HCC 患者对药物的反应不佳。如何减轻甚至逆转 CDDP 耐药性是一个亟待解决的临床问题。由于在生物功能过程和疾病发展中发挥着关键作用,近年来非编码 RNA (ncRNA) 在 HCC 中得到了广泛研究。重要的是,ncRNA 也被证明参与了 HCC 向 CDDP 耐药性发展的过程。因此,本综述强调了 ncRNA 在 HCC 对 CDDP 耐药性中的调控作用,阐明了 HCC 产生 CDDP 耐药性的多种潜在机制,并尝试提出多种药物递送系统来减轻 CDDP 耐药性。最近,基于 ncRNA 的治疗可能是减轻 HCC 中 CDDP 耐药性的一种可行策略。同时,纳米颗粒可以克服基于 ncRNA 的治疗的缺陷,使逆转肿瘤耐药性成为可能。这些策略的联合使用为逆转 CDDP 耐药性和克服 HCC 预后不良提供了线索。

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