丹参及其提取物治疗口腔恶性肿瘤药理机制研究进展

Research progress on pharmacological mechanism of Salvia miltiorrhiza and its extracts in the treatment of oral malignant tumors

丹参的主要提取物包括丹参酮、丹酚酸、隐丹参酮、丹参素等,其中丹参酮ⅡA可抑制肿瘤细胞有氧糖酵解进程,以阻止肿瘤细胞增殖;丹酚酸B和丹参酮ⅡA可通过抑制磷脂酰肌醇三羟基激酶/蛋白质丝氨酸苏氨酸激酶(phosphoinositide-3 kinase/serine threonine kinase, PI3K/Akt)信号通路传导,促进口腔鳞状细胞癌肿瘤细胞凋亡;丹酚酸B和丹参酮ⅡA可通过下调环氧合酶-2(cyclooxygenase 2,COX-2)/B淋巴细胞瘤-2基因(B-cell lymphoma-2,Bcl-2)的表达,有助于降低头颈部鳞状细胞癌和鼻咽癌的炎症状态,以促使细胞凋亡;丹酚酸B能通过抑制蛋白质丝氨酸苏氨酸激酶/雷帕霉素靶蛋白(serine threonine kinase/Mammalian target of rapamycin, Akt-mTOR)信号通路传导,促使口腔白斑癌变线粒体凋亡和肿瘤细胞凋亡;丹参提取物能激活并提高半胱天冬酶-3(caspase-3)的活性,促使口腔癌耐药细胞凋亡;隐丹参酮可通过抑制Janus激酶/信号传导和转录激活因子3(janus kinase/signal transducers and activators of transcription 3,JAK/STAT3)信号通路的信号传导,促使舌鳞状细胞癌肿瘤细胞凋亡;丹酚酸A和丹参素可通过抑制基质金属蛋白酶2(matrix metalloproteinase 2,MMP-2)的表达,降低肿瘤细胞的侵袭和迁移;丹酚酸B能抑制缺氧诱导因子1α的表达,降低血管内皮细胞和微血管密度水平,抑制口腔癌血管的形成。本文旨在探讨丹参及其提取物治疗口腔恶性肿瘤的药理机制,为临床研究提供参考。

The main extracts of Salvia miltiorrhiza include tanshinone,salvianolic acid,cryptotanshinone,tanshinol and so on.Tanshinone IIA can inhibit the aerobic glycolysis process of tumor cells and prevent the proliferation of tumor cells.Salvianolic acid B and tanshinone IIA can promote apoptosis of oral squamous cell carcinoma tumor cells by inhibiting phosphatidylinositol trihydroxy kinase/protein serine threonine kinase(PI3K/Akt)signaling pathway.Salvianolic acid B and tanshinone IIA can reduce the inflammatory state of head and neck squamous cell carcinoma(HNSCC)and nasopharyngeal carcinoma by down regulating the expression of cyclooxygenase-2(COX-2)/B-cell lymphoma-2 gene(Bcl-2).Salvianolic acid B can promote mitochondrial apoptosis and tumor cell apoptosis in oral Leukoplakia Carcinogenesis by inhibiting the signal transduction of Akt/mammary target of rapamycin(mTOR).Salvia miltiorrhiza extract can activate and enhance the activity of Caspase-3 and promote the apoptosis of drug-resistant oral cancer cells.Cryptotanshinone can promote the apoptosis of tongue squamous cell carcinoma tumor cells by inhibiting the signaling of Janus kinase/signal transducers and activators of transcription 3(JAK/STAT3)signaling pathway.Salvianolic acid A and danshensu can reduce the invasion and migration of tumor cells by inhibiting the expression of matrix metalloproteinase 2(MMP-2).Salvianolic acid B can inhibit the expression of HIF-1α.It can reduce the density of vascular endothelial cells and microvessels and inhibit the formation of blood vessels in oral cancer.The purpose of this paper is to explore the pharmacological mechanism of Salvia miltiorrhiza and its extract in the treatment of oral malignant tumors,so as to provide references for clinical research.