| Salvia miltiorrhiza is a kind of perennial medicinal herb,and it’s dry root and rhizome is used as traditional Chinese medicine in China,which is also called Danshen.Danshen was first published in Shennong herbal classic and now is mainly cultivated in Sichuan,Shandong,Henan,and Shanxi in China.It’s tasted bitter,slightly cold,heart,liver meridian,and has the effect of promoting blood circulation,promoting blood circulation,removing blood stasis,relieving pain and clearing heart,especially has therapeutic effect on dysmenorrhea,accumulation of symptoms,swelling and pain of sores,chest and abdominal pain,restlessness,angina pectoris and other diseases.Tanshinone IIA,cryptotanshinone and tanshinone I are the mainly lipid soluble components used for quality control in Chinese pharmacopoeia(2015,part I),and the content of tanshinone IIA was the highest,cryptotanshinone was the second,and tanshinone I(Tan-Ⅰ)was the lowest.Due to the low content of tanshinone I,there is few study on its pharmacological effects.Ovarian cancer is a common gynecological malignant tumor,90%-95% of which are primary ovarian cancer.Because ofinsidious symptoms and difficult clinical screening,most patients are diagnosed as advanced cancer and missed the best treatment time.At present,ovarian cancer has become a serious disease that influenced women’s physical and mental health.Fortunately,high purity tanshinone I monomer has been isolated in our laboratory,and preliminary tests have shown that tanshinone I has anti-ovarian cancer activity.Therefore,in this study,tanshinone I was selected to analysis its extraction technology and the effect of anti-tumor effect.The main results are as follows:1.In this study,ovarian cancer cell lines A2780 and ID-8 were used as models to analyze the effects of Tan-Ⅰ on proliferation,apoptosis,invasion,migration and epithelial mesenchymal transition of ovarian cancer cells.The results showed that Tan-Ⅰ significantly inhibited the proliferation,invasion and migration of A2780 and ID-8 cells and promoted the apoptosis of ovarian cancer cells in a dose-dependent manner.Tan-Ⅰ had no effect on epithelial mesenchymal transition of tumor cells.2.Tan-Ⅰ significantly induced cell autophagy in A2780 and ID-8 cells,promoted the expression of Beclin1 and ATG7,the degradation of p62 and the transformation of LC3-I to LC3-II.The molecular mechanism showed that Tan-Ⅰ can promote autophagy by down regulating the phosphorylation levels of PI3 K,Akt and m TOR.3.Ovarian cancer cell line A2780 was inoculated into axillary fat pad of nude mice to establish tumor model.The results showed that Tan-Ⅰ(30 mg/kg)could significantly inhibit the growth of tumor in mice,and had no side effects.Compared with the control group,the expression level of Caspase-3 and the positive rate of TUNEL staining were significantly increased in Tan-Ⅰ group.The expression levels of autophagy proteins Beclin1 and ATG7 were significantly increased and the autophagy activity was significantly increased.Tan-Ⅰ inhibits tumor growth in vivo by promoting tumor cell apoptosis and autophagy.4.In order to improve the anti-tumor effect of Tan-Ⅰ,this study combined tan-I with paclitaxel(PTX)in the treatment of ovarian cancer.In vitro,the results showed that the combination of Tan-Ⅰ and PTX could significantly inhibit the proliferation and migration of ovarian cancer cells.The combination of Tan-Ⅰ and PTX could significantly promote tumor cell apoptosis by activating Caspase-3 and increasing the ratio of Bcl-2/Bcl-2and tumor cell senescence by up-regulating the expression levels of γ-H2 AX,p21 and p16 protein.Antitumor studies in vivo have shown that tan-I combined with PTX can significantly inhibit the growth of ovarian cancer. |
PDF Full Text Request