Anti-tumor Effect Of Dihydrotanshinone ? On Ovarian Cancer Through The Inhibition Of Cell Metastasis

Background: Ovarian cancer is a kind of malignant tumor of ovarian tumor.It is difficult to diagnose in early stage.At present,the effective means of ovarian cancer treatment is radiotherapy,chemotherapy and surgical treatment.Chemotherapy is the most widely useful and the most important treatment for ovarian cancer.Cisplatin is commonly used in clinic for chemotherapy,cisplatin get the body tissues and organs through blood circulation,resulting in DNA damage to kill cancer cells.But cisplatin will produce a series of cell toxicity in human normal cells and be damage to the immune system of human body,in addition,the cancer cells can be resistant to cisplatin,therefore,finding an effective drugs against ovarian cancer and having no toxicity for normal cells are significance important.Dihydrotanshinone I is extract from Danshen rhizome,Salvia is commonly used in clinic,it is reported Salvia miltiorrhiza can increase coronary blood flow,coronary artery dilatation,prevent the cardiovascular effects of myocardial ischemia,as well as for the treatment of gastric cancer,liver cancer,cervical cancer and other diseases.Dihydrotanshinone I is the most important anti-tumor component extracted from Salvia miltiorrhiza Bunge,and the effect of Dihydrotanshinone I on normal human cells is less than on cancer cells,but the anti-tumor effect mechanism of Dihydrotanshinone I is still not clear.Objective: This study is mainly detect the anti-ovarian cancer cells effects of Dihydrotanshinone,to prove the inhibition mechanism of Dihydrotanshinone I is inhibition of the proliferation and metastasis in ovarian cancer,provide a new strategy for clinical treatment of ovarian cancer.Methods: 1.MTT assay was used to detect the growth and proliferation of A2780 and OV2008 cells in vitro.2.The effect of Dihydrotanshinone I on A2780 and OV2008 cells were detected by wound healing and invasion test in vitro.The effect of Dihydrotanshinone I on the metastatic ability of the cells was evaluated.3.The gene changes of A2780 cells after treatment with of Dihydrotanshinone I were detected by gene chip technique.4.According to the gene sequence of the target gene PIK3 CA,the specific over expression plasmid and unrelated(NC)sequences were designed.Plasmid were transfected into A2780 cells by lipofectamin2000 liposome,and the over-expression of PIK3 CA was detected by Western blot.5.q PCR and Western blot methods were used to detect the expression of m RNA and protein expression of the target genes.6 To detect the changes of A2780 cells and PIK3 CA cell growth and proliferation of A2780 cells were compared by MTT assay and clone formation assay in vitro.7 To compare the ability of A2780 cells and PIK3 CA A2780 cells by scratch and invasion test.Results: 1.Dihydrotanshinone I inhibited the proliferation of A2780 and OV2008 cells by using MTT,and the inhibitory effect was time-and dose-dependent.2 The results of wound healing and invasion test showed that the effect of Dihydrotanshinone I on the inhibition of A2780 and OV2008.3 Microarray results showed that DDB2,HGF and other related genes such as PIK3 CA were down regulated after the treatment with Dihydrotanshinone I.4 Using over exprssion plasmid technique,the PIK3 CA expression up regulated cell model was successfully obtained,and the expression of PIK3 CA was up regulated in the cells of group,which was significantly higher than that of the control group.5.The the inhibitory effect by Dihydrotanshinone I of the over-expression PIK3 CA group was lower than that of the control group.Conclusion: The results suggest that Dihydrotanshinone I can inhibit the proliferation and metastasis of ovarian cancer cells by inhibiting the expression of PI3K/AKT by PIK3 CA.Dihydrotanshinone I has potential clinical significance in the treatment of cancer.