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The Study Of β-elemene Combine With Olaparib In Ovarian Cancer

Posted on:2022-01-04Degree:MasterType:Thesis
Country:ChinaCandidate:Y Q GuoFull Text:PDF
GTID:2504306335977099Subject:Biomaterials and Medicinal Chemistry
Abstract/Summary:PDF Full Text Request
Ovarian cancer is one of the gynaecological tumor with a high incidence and is on the rise.On the other hand,most patients are diagnosed with ovarian cancer at an advanced stage,and treatment to prolong survival is also a challenge.PARP(polyadenosine diphosphate ribose polymerase)inhibitors have become popular chemotherapy regimens for the treatment of cancer in recent years because of their ability to inhibit DNA damage repair.As one of these orders,olaparib is mainly used in the clinical treatment of ovarian cancer and breast cancer,which has obvious effects,but also has relatively large toxic and side effects.In addition,some ovarian cancer patients will develop drug resistance after a period of treatment.Therefore,it is necessary to find a drug that can be combined with olaparib to reduce the side effects and reverse developmented resistance in ovarian cancer cells.It is known thatβ-elemene can be used clinically as a secondary anti-tumor drug.It has been reported in number of studies that it can combine with a variety of anti-tumor drugs,and has a good synergistic effect.In addition,elemene has also been shown to reverse drug resistance in tumor cells.Therefore,this study aims to initially explore the synergistic effect of the auxiliary drug β-elemene and olaparib in ovarian cancer cells,and to explore the ability of β-elemene of reversing olaparib resistance in ovarian cancer cells.Provide some medication basis for how to reduce the side effects of olaparib and the clinical use of olaparib in the future.Firstly,to investigate the synergistic effect of β-elemene combined with olaprib,cytotoxicity assay,colon formation assay,EDU proliferation assay,cell flow cycle assay,western-blot assay were done,and the ovarian cancer cells used in these assay were treated with β-elemene and or olaprib for several hours.All the above results suggested that the combination of β-elemene and olaparib would show a synergistic effect on ovarian cancer as a chemotherapy treatment.These analysis also revealed that olaparib alone can significantly inhibited PARP,and co-treatment of olaparib with β-elemene led to further increase of cleaved PAPR level,inhibition of cell proliferation ability and percentage apoptotic cells.Therefore,the combination of β-elemene with olaparib could reduce dosage of oalparib and induce more ovarian cancr cells apoptosis compare to the same concentration of olaparib.Secondly,to examinated weather β-elemene could reverse olaparib resistance in ovarian cancer,colon formation assay,TUNEL assay,cell apoptosis assay,western-blot assay,q-RT-PCR assay were applied.To the conclusion,the tumor response to olaparib although the same dosage was used in all experiments,the response in the co-treated with β-elemene experiment was much higher compared to the non-treated with β-elemene.And the machanism of β-elemene restores the sensitivity of ovarian cancer to olaparib is based on recalling the level of CAPG.Therefore,the combination of β-elemene and olaparib can reduce the use of olaparib to a certain extent and induce more ovarian cancer cell apoptosis.When ovarian cancer cells develop resistance to olaparib,β-elemene can reverse the resistance of ovarian cancer cells to olaparib.
Keywords/Search Tags:β-elemene, olaparib, ovarian cancer, combination index
PDF Full Text Request
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