熊果酸在肿瘤治疗中的研究进展

Advancement for the Study of Ursolic Acid on Anti-tumor

熊果酸(ursolic acid)是广泛存在于自然界植物中的一种五环三萜类化合物,具有广泛的生物学活性,主要经肝脏代谢。传统临床治疗中熊果酸多用于抗炎、抗病毒、调节免疫功能以及保肝治疗等。近年来的研究表明,在体外和体内实验中,熊果酸能够对不同肿瘤细胞产生杀伤作用,抑制恶性肿瘤组织的生长,具有广谱的抗肿瘤活性。此外,熊果酸联合放化疗能够提高肿瘤细胞对治疗的敏感性,产生辅助增强放化疗疗效的作用,并且在放疗中可保护受照射机体的正常组织,促进免疫机能的恢复。熊果酸的抗肿瘤作用机制与下调促肿瘤生长、侵袭和转移相关基因的水平,增强凋亡基因的表达有关,并且能够通过调节多种细胞信号转导通路,杀灭肿瘤细胞,延缓肿瘤组织生长。同时,熊果酸可影响肿瘤细胞周期的分布,导致细胞的G1/S期阻滞,从而抑制肿瘤细胞的有丝分裂,诱导细胞凋亡。因此,熊果酸是一种极具潜力的天然抗肿瘤药物。本文对熊果酸在肿瘤治疗中的研究结果进行整合,阐述了熊果酸的抗肿瘤分子机制及其疗效,为熊果酸今后在临床中的进一步应用提供指导思路。

Ursolic acid belongs to the pentacyclic Iriterpenoid family, which is widely distributed in the plant kingdom. It has an extensive range of biological activity, including anti-inflammatory, anti-viral, promoting immune function, protecting liver and so on, followed by discharging via liver metabolism. In recent years, a number of studies have shown that ursolic acid could effectively inhibit the growth of several malignant tumor tissue and ceils in vitro and in vivo. Moreover, the sensitivity of tumor cells to radio-chemotherapy may be increased by ursolic acid pretreatment. Furthermore, curative effect of an-nor therapy could be elevated through the combination of ursolic acid and radio-chemotherapy. And normal tissue exposure to irradiation could be protected by ursolic acid treatment. The mechanism of the anti-tumor effect of ursolic acid was demonstrated that the levels of the pro-growth, invasion and metastasis of genes were reduced by ursolic acid treatment; meanwhile the expression of proapoptotic gene was up-regulated. Various intracellular signal transduction pathways regulated by ursolic acid could be also contributed to the inhibition of tumor cells and tissue. On the other hand, ursolic acid might influence cell cycle of turnor cell to inducing the delay of G1/S phase, followed by blocking mitosis and promoting the apoptosis of tumor cells. In order to boost the clinical utilization of ursolic acid, recent studies and reports about the curative effect of ursolic acid on cancer were summarized in this review.