Study On The Therapeutic Effect And Mechanism Of Panaxadiol On Ovarian Cancer

Ovarian cancer（OC）is one of the most common malignant tumors in the female reproductive system.Its incidence ranks after cervical cancer and endometrial cancer,and its mortality ranks first among gynecological tumors.Surgery combined with platinum-based chemotherapy is a common treatment for ovarian cancer.Because ovarian cancer is easy to develop chemotherapy resistance and high side effects of platinum chemotherapy drugs,the five-year survival rate of patients is very low.Therefore,it has become an urgent problem for us to find new anti-ovarian tumor drugs with high efficiency,new type and low side effects in order to improve the therapeutic effect and prognosis of ovarian cancer.At present,ginseng is recognized as a good anticancer drug,which can enhance the anti-disease function and improve the immune function.Many single products of ginseng have been studied on tumor.In the previous work of the research group,the active components of Panax ginseng were analyzed by using the traditional Chinese medicine system pharmacology database,and the corresponding targets of the active components were predicted by constructing the drug target similarity model.finally,22active components and 96 potential targets in ginseng were obtained.Because panaxadiol is a unique active ingredient of Panax ginseng and is related to apoptosis pathway and the treatment of cancer,panaxadiol is selected as this drug study.By consulting some literatures,it is found that panaxadiol has shown anti-tumor activity in other tumor cells,but the specific mechanism is not clear.Based on network pharmacology and literature investigation,we believe that PPD may transmit signals to the Bcl-2 family related to apoptosis by regulating related pathways,and finally cause a series of changes in mitochondria,leading to apoptosis.We think that this effect may be a mechanism of PPD as an anticancer drug.Research objectives:To clarify the important role of ovarian cancer cells sensitive to panaxadiol and reveal the related mechanism that panaxadiol can induce the death of ovarian cancer cells,in order to provide theoretical and experimental basis for the treatment mechanism of patients with ovarian cancer.Methods and results:1.It is clear that PPD has killing effect on ovarian cancer cells.Taking ovarian cancer cells as the research object,the effects of two different configurations of panaxadiol on the activity of ovarian cancer cells such as SKOV3,ES-2,A2780 and NIH-ovcar3 were investigated by MTT method,and the IC₅₀ was calculated.The results showed that among all kinds of cells tested,panaxadiol had the highest sensitivity to the survival rate of A2780 ovarian cancer cells,and the IC₅₀ was lower.The results showed that ovarian cancer cell line A2780 was more sensitive to panaxadiol.2.Panaxadiol can induce apoptosis of ovarian cancer cells.Using ovarian cancer cell line A2780 as a model,the effect of panaxadiol on apoptosis was studied by flow cytometry.The results showed that obvious apoptosis occurred in ovarian cancer cell line A2780 after panaxadiol treatment.On this basis,the effect of panaxadiol on apoptosis pathway of ovarian cancer cell line A2780 was detected by Caspase-3,-8,-9 kit.The results showed that panaxadiol significantly increased the enzyme activity of Caspase-3,-8,-9 in ovarian cancer cell line A2780.On the basis of this experiment,the effect of panaxadiol on the m RNA expression of Bcl-2 family in ovarian cancer cell line A2780 was analyzed by fluorescence quantitative RT-PCR.The results showed that panaxadiol could significantly down-regulate the expression of m RNA such as Bcl-xl and Bcl-2,and up-regulate the expression of m RNA such as BAK and BIK in ovarian cancer cells.3.Panaxadiol can inhibit the invasion and migration of ovarian cancer cells.Ovarian cancer cell line A2780 was used as a model by cell scratch test,Transwell migration and.Invasion experiment and other methods were used to explore the invasion and migration ability of tumor cells under the action of drugs.The results showed that the healing ability of ovarian cancer cells treated with panaxadiol was significantly lower than that of the control group,and the invasion and migration ability of ovarian cancer cells was significantly weakened.4.Panaxadiol can obviously inhibit the growth of tumor.Ovarian cancer cell line A2780 was used for tumor transplantation in nude mice,and the tumor volume was measured after panaxadiol was given to observe the anti-tumor effect of panaxadiol.The changes of m RNA expression of Bcl-2 family after panaxadiol treatment were compared by fluorescence quantitative RT-PCR,and immunohistochemical experiment was used to explore the apoptosis of tumor after panaxadiol treatment.The results showed that panaxadiol could effectively inhibit the growth of transplanted ovarian cancer in nude mice,down-regulate the expression of m RNA such as Bcl-xl and Bcl-2,and significantly up-regulate the expression of m RNA such as BAK and BIK,and promote the occurrence of tumor apoptosis.The difference was statistically significant.Conclusion:This study revealed the sensitivity of ovarian cancer cells to panaxadiol at the cellular and animal level,and confirmed that the enzyme activity of ovarian cancer cell line Caspase-3,-8,-9 increased after drug treatment,and activated the apoptosis pathway,which will provide new ideas and new drugs for improving the treatment of clinical ovarian cancer patients.