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Study On The Effect Of Vorinostat Combined With Veliparib On Human Triple Negative Breast Cancer Cells

Posted on:2022-09-13Degree:MasterType:Thesis
Country:ChinaCandidate:J H HuangFull Text:PDF
GTID:2504306542995109Subject:Surgery
Abstract/Summary:PDF Full Text Request
Background and objectiveBreast Cancer(BC)is the most common malignant tumor in women.Its Morbidity and mortality rate is the highest among female-related cancers,which brings a heavy burden to the global health economy.Triple negative breast cancer(TNBC)is a special subtype of breast cancer,accounting for 10%-15% of all types of breast cancer.It is characterized by high malignancy,high recurrence rate and metastasis rate,high resistance to chemotherapy and poor prognosis.At present,TNBC is mainly treated by surgery and chemotherapy.However,50% of patients who have tumor resection and complete radiotherapy and adjuvant chemotherapy still have recurrence due to chemotherapy resistance.However,with the development of research,the therapeutic potential of targeted therapy in TNBC appears gradually.Histone deacetylase(HDAC)inhibitors and Poly ADP-ribose polymerase(PARP)inhibitors can both promote DNA damage and inhibit DNA repair to induce cancer cell apoptosis,it is one of the most promising target drugs for breast cancer.In this study,we treated triple-negative human breast cancer cells with histone deacetylase(HDAC)inhibitor Vorinostat(SAHA),Poly ADP-ribose polymerase(PARP)inhibitor Veliparib and a combination of both,and then observe the cell viability,migration and invasion,and apoptosis of cancer cells was analyzed using Flow cytometry.Finally,the effects of SAHA,Veliparib and their combination on cell function and apoptosis of breast cancer cells were analyzed by statistical methods.Methods1.Cell viability test showed that the growth inhibition rate of breast cancer cells treated with SAHA or Veliparid alone did not decrease with the increase of the concentration of the drug(P<0.05),while the combination of SAHA and Veliparib significantly increased the growth inhibition rate of breast cancer cells,and the growth inhibition rate decreased with the concentration increase,the difference was statistically significant(P<0.05);2.The results of cell migration test showed that the migration ability of breast cancer cells decreased significantly with the increase of drug concentration(P<0.05),and the migration ability of SAHA combined with Veliparib was significantly lower than that of single drug group(P<0.05).3.The results of cell invasion test showed that the invasion ability of breast cancer cells decreased significantly with the increase of drug concentration(P<0.05),and the invasion ability of SAHA combined with Veliparib was significantly lower than that of the single drug group(P<0.05).4.The results of Flow cytometry showed that SAHA or Veliparib alone did not significantly promote the apoptosis of breast cancer cells,and the apoptosis rate did not increase with the increase of concentration of the drug(P>0.05),while the two drugs were used together,the apoptotic effect on the breast cancer cells was greatly enhanced,and the apoptotic rate increased with the increase of the concentration of these drugs,the difference was statistically significant(P<0.05).Conclusion1.SAHA or Veliparib alone had a weak inhibitory effect on the growth of triple negative breast cancer cells in vitro,but the combination of SAHA or Veliparib could significantly inhibit the growth of triple negative breast cancer cells.2.SAHA or Veliparib can obviously inhibit the migration and invasion of human triple negative breast cancer cells in vitro,and the combination of SAHA or Veliparib can further enhance this inhibitory effect;3.SAHA or Veliparib alone had no significant effect on the apoptosis of breast cancer cells,but the combination of SAHA or Veliparib showed a strong pro-apoptotic effect.
Keywords/Search Tags:Human triple-negative breast cancer, HDAC inhibitor, PARP inhibitor, Targeted therapy
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