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1.上海交通大学 附属第六人民医院,上海 200030
2.上海海洋大学 食品学院,上海 200135
Received:28 December 2021,
Published Online:12 March 2022,
Published:05 September 2022
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孔欠文,陈君君,胡玉洁等.中药单体逆转紫杉醇耐药作用机制的研究进展[J].中国实验方剂学杂志,2022,28(17):209-216.
KONG Qianwen,CHEN Junjun,HU Yujie,et al.Mechanism of Chinese Medicine Monomer Reversing Paclitaxel Resistance: A Review[J].Chinese Journal of Experimental Traditional Medical Formulae,2022,28(17):209-216.
孔欠文,陈君君,胡玉洁等.中药单体逆转紫杉醇耐药作用机制的研究进展[J].中国实验方剂学杂志,2022,28(17):209-216. DOI: 10.13422/j.cnki.syfjx.20220928.
KONG Qianwen,CHEN Junjun,HU Yujie,et al.Mechanism of Chinese Medicine Monomer Reversing Paclitaxel Resistance: A Review[J].Chinese Journal of Experimental Traditional Medical Formulae,2022,28(17):209-216. DOI: 10.13422/j.cnki.syfjx.20220928.
紫杉醇是多种癌症的一线化疗药物,但其耐药性的产生使得其后期治疗疗效大大降低,增加了癌症患者的死亡率及复发率,严重限制了其临床应用。目前,临床上的一些中药复方、中成药、中药注射液等辅助化疗药物治疗癌症患者的应用已十分广泛,中药在提高化疗药物疗效、降低化疗不良反应及改善预后等方面均展示出独特的优势,但其发挥逆转化疗药物耐药的作用机制及有效单体成分尚未明确,在不同癌症类型的应用方面也十分局限,值得进一步挖掘和探究。该文总结了近年与紫杉醇联用具备协同抗肿瘤疗效的中药单体成分,并分类列举了其发挥逆转紫杉醇耐药作用的具体机制及药理活性,发现中药单体不仅通过作用于膜转运蛋白促进紫杉醇在肿瘤细胞内的蓄积、抑制多药耐药相关蛋白及代谢酶表达抑制紫杉醇的代谢、调控细胞凋亡基因、因子水平及凋亡相关通路促进紫杉醇发挥细胞增殖抑制作用,还可通过调控微小RNA(microRNA)及长链非编码RNA(lncRNA)表达水平、抑制肿瘤干细胞特性及肿瘤代谢重编程、改善肿瘤微环境、触发肿瘤细胞死亡性自噬及氧化应激反应等方面显著提高紫杉醇的化疗敏感性,为明确中药单体联合紫杉醇抗肿瘤的具体机制提供理论基础,对中药新药开发及临床寻找紫杉醇的联合用药具有重要意义,也对中药与其他化疗药物联合应用的探究具有一定参考价值。
Paclitaxel is the first-line chemotherapy drug for a variety of cancers. However, the paclitaxel resistance greatly reduced the efficacy in the later treatment stage, which seriously increased the mortality and recurrence rate of cancer and limited the clinical application of paclitaxel. At present, Chinese medicine compound prescription, proprietary Chinese medicine, and Chinese medicine injection are widely used as the adjuvant chemotherapy drugs for the treatment of cancer in clinic. Chinese medicine has shown unique advantages in improving the efficacy of chemotherapy drugs and the prognosis of chemotherapy, and reducing the toxic and side effects. However, the specific mechanism and effective monomer composition of Chinese medicine for reversing the resistance of chemotherapy drugs are unclear, and the application of Chinese medicine in different types of cancer is also limited, which are worthy of further exploration. This review summarized the composition of Chinese medicine monomer with synergistic antitumor effect combined with paclitaxel in recent years. The specific mechanism and pharmacological activities of Chinese medicine monomer reversing paclitaxel resistance were classified. This review found that through acting on the membrane transport protein, Chinese medicine monomer promoted the accumulation of paclitaxel in tumor cells, inhibited the expressions of protein and metabolic enzyme related to multidrug resistance and the metabolism of paclitaxel, and regulated the levels of apoptosis genes and factors and apoptosis-related pathways to promote the inhibitory effect of paclitaxel on cell proliferation. Chinese medicine monomer also significantly improved paclitaxel chemotherapy sensitivity by regulating the expression levels of micro ribonucleic acid (microRNA) and long non-coding ribonucleic acid RNA (lncRNA), inhibiting the characteristics of tumor stem cells and tumor metabolic reprogramming, improving tumor microenvironment, and triggering tumor cell death autophagy and oxidative stress response. This review provides a theoretical basis for clarifying the specific anti-tumor mechanism of Chinese medicine monomer combined with paclitaxel, which is of great significance for the development of new Chinese medicine and the clinical research of the drugs combined with paclitaxel, and has certain value for the application of Chinese medicine combined with other chemotherapy drugs.
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