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1.甘肃中医药大学 基础医学院,兰州 730000
2.甘肃省中医药防治慢性疾病重点实验室(培育基地),兰州 730000
3.甘肃省高校重大疾病分子医学与中医药防治研究省级重点实验室,兰州 730000
Received:19 July 2022,
Published Online:21 November 2022,
Published:20 June 2023
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赵玉,龙凤,刘晓燕等.鸦胆子素D抗肿瘤作用机制的研究进展[J].中国实验方剂学杂志,2023,29(12):274-282.
ZHAO Yu,LONG Feng,LIU Xiaoyan,et al.Anti-tumor Mechanisms of Bruceine D: A Review[J].Chinese Journal of Experimental Traditional Medical Formulae,2023,29(12):274-282.
赵玉,龙凤,刘晓燕等.鸦胆子素D抗肿瘤作用机制的研究进展[J].中国实验方剂学杂志,2023,29(12):274-282. DOI: 10.13422/j.cnki.syfjx.20230124.
ZHAO Yu,LONG Feng,LIU Xiaoyan,et al.Anti-tumor Mechanisms of Bruceine D: A Review[J].Chinese Journal of Experimental Traditional Medical Formulae,2023,29(12):274-282. DOI: 10.13422/j.cnki.syfjx.20230124.
恶性肿瘤严重威胁着人类的生命健康。放疗和化疗是目前临床治疗晚期肿瘤的常规方法,由于放疗对机体不良反应严重、化疗常引起肿瘤耐药性和细胞增殖抑制作用等问题,其预后和疗效不尽人意。因此寻找新型安全有效的抗肿瘤药物、阐明药物抗肿瘤分子作用机制是临床治疗肿瘤和改善患者生活质量的有效措施。源于中草药及天然产物的有效活性成分因其具多靶点、多途径的抗肿瘤药理活性特点,且其对机体不良反应小等优点而逐渐成为抗肿瘤药物研发的热点。鸦胆子素D是从鸦胆子果实中提取的一类四环三萜类化合物,不仅具有抗炎、抗疟、抗寄生虫等多种药理学活性作用,其抗肿瘤活性尤为显著。药理学研究发现,鸦胆子素D可通过靶向不同的信号通路来调控肺癌、肝癌、胰腺癌、肠癌等多种癌细胞的增殖、凋亡、侵袭和迁移等多种细胞生理活动;鸦胆子素D还可与其他化疗药物联用提高肿瘤细胞对化疗药物的敏感性,从而减轻化疗的不良反应。临床应用实践已表明,含有鸦胆子素D的鸦胆子油乳注射液在肿瘤治疗的有效性和安全性方面具有显著的优越性。虽鸦胆子素D的抗肿瘤药理学活性研究较多、临床功效作用显著,然而鸦胆子素D的具体抗肿瘤分子机制仍不清楚,且缺乏对现有鸦胆子素D抗肿瘤作用机制研究的系统性综述。因此,笔者依据近年来国内外对鸦胆子素D的研究,从肿瘤细胞的增殖、凋亡、转移和侵袭、糖代谢过程、自噬以及化疗敏感性等6个方面对鸦胆子素D抗肿瘤作用及相关分子机制的研究进行综述,以期为鸦胆子素D的抗肿瘤药物研发和临床应用提供药理学依据和科学参考。
Malignant tumors seriously threaten human life and health. Radiotherapy and chemotherapy are the conventional methods for the clinical treatment of advanced tumors. The prognosis and efficacy are still far from satisfactory due to the radiotherapy has serious adverse effects on the body and the chemotherapy often causes problems such as tumor resistance and cell proliferationinhibition. Therefore, the search for new, safe, and effective anti-tumor drugs and the elucidation of their molecular mechanisms are effective measures for clinical treatment of tumors and improvement of patients' quality of life. Active ingredients derived from Chinese herbal medicines and natural products have gradually become a hot spot in the research and development of anti-tumor drugs due to their multi-target and multi-channel anti-tumor pharmacological activity characteristics and their advantages such as less adverse reaction on the body. Bruceine D is a class of tetracyclic triterpenoids extracted from the fruit of the Chinese herbal medicine Bruceae Fructus, with anti-inflammatory, anti-malarial, anti-parasitic, and other pharmacological activities, and its anti-tumor activity is particularly significant. Pharmacological studies have found that bruceine D can regulate various cellular physiological activities such as proliferation, apoptosis, invasion, and migration of lung cancer, liver cancer, pancreatic cancer, intestinal cancer, and other cancer cells by targeting different signaling pathways. Bruceine D can be used in combination with other chemotherapeutic drugs to improve the sensitivity of tumor cells to chemotherapeutic drugs, thereby reducing the adverse effect of chemotherapy. Clinical application practice has shown that Bruceae Fructus oil emulsion injection containing bruceine D has significant advantages in the efficacy and safety of tumor treatment. Although there are many studies on the antitumor pharmacological activity of bruceine D and its clinical efficacy is significant, the specific antitumor molecular mechanism of bruceine D is still unclear, and there is a lack of systematic review on the existing antitumor mechanism of bruceine D. Therefore, based on the research on bruceine D in China and abroad in recent years, this paper reviewed the anti-tumor effect and related molecular mechanisms of bruceine D from six aspects, namely, tumor cell proliferation, apoptosis, metastasis and invasion, glucose metabolism process, autophagy, and chemotherapy sensitivity. This paper is expected to provide a pharmacological basis and scientific reference for the antitumor drug development and clinical application of bruceine D.
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