表观遗传学改变与中药活性成分靶向抗肿瘤的研究进展

Research progress on epigenetic changes and targeted anti-tumor effects of traditional Chinese medicine active ingredients

  • 摘要: 表观遗传学在癌症临床治疗和预防中占据重要地位。表观遗传学改变如DNA甲基化、组蛋白修饰、非编码RNA (ncRNA)、染色质结构重塑等是基于对DNA碱基序列以外的基因调控, 不影响DNA的碱基序列。表观遗传改变通过调控抑癌或促癌基因转录或相关基因的表达、沉默或DNA复制和修复或端粒调节、着丝粒稳定性、染色体分离等过程参与临床恶性肿瘤的多种生物学过程,常被应用于早期恶性肿瘤的临床诊断和预后检测。因此,针对表观遗传改变的药物广泛应用于多种恶性肿瘤的临床治疗,但仍存在耐药性、不良反应及应答率低等问题,极大地影响患者生活质量和预后。中医药在恶性肿瘤治疗上疗效显著,多通路、多分子、多靶点的中药活性成分的抗肿瘤作用机制成为研究热点,基于表观遗传学改变的抗肿瘤中药或联合表观遗传改变的药物对恶性肿瘤的治疗具有重要临床价值。本文从表观遗传学改变与相关药物、基于表观遗传学改变抗肿瘤作用、中药活性成分通过调节甲基转移酶(DNMT)、组蛋白修饰、ncRNA、染色质结构重塑和靶向抗肿瘤等方面对中药活性成分的抗肿瘤机制进行综述,以期从表观遗传学改变角度为抗肿瘤中药新药的研究提供思路。

     

    Abstract: Epigenetics occupies an important position in the clinical treatment and prevention of cancer. Epigenetic changes such as DNA methylation(DNMT), histone modification, non-coding RNA (ncRNA), and chromatin structural remodeling, and chromatin remodeling are based on gene regulation beyond the DNA base sequence and do not affect the DNA base sequence. Epigenetic changes are involved in a variety of biological processes of clinical malignant tumors by regulating the transcription of tumor suppressor or cancer-promoting genes or the expression of related genes, silencing or DNA replication and repair, telomere regulation, centromeric stability, chromosome separation and other processes, and are often applied in the clinical diagnosis and prognosis of early malignant tumors. Therefore, drugs targeting epigenetic changes are widely used in the clinical treatment of various malignant tumors, but there are still problems such as drug resistance, adverse reactions and low response rates, which greatly affect the quality of life and prognosis of patients. Traditional Chinese medicine has a unique clinical effect in the treatment of malignant tumors, and the anti-tumor mechanism of active ingredients of traditional Chinese medicine with multiple pathways, multiple molecules and multiple targets has become a research hotspot. Anti-tumor research is still rare, and anti-tumor traditional Chinese medicines based on epigenetic changes or drugs combined with epigenetic changes have important clinical value for some malignant tumors. This paper discussed epigenetic changes and related drugs, anti-tumor based on epigenetic changes, and active components of traditional Chinese medicine by regulating DNA methylation (DNMT), histone modification, ncRNA, chromatin structure remodeling, and targeted antitumor, etc, in order to provide ideas for the research and development of new traditional Chinese medicine drugs targeting anti-tumor from the perspective of epigenetic changes.

     

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