Effect Of Dexamethasone On The Efficacy Of Doxorubicin And Docetaxel In Breast Cancer TAC Or AC-T Chemotherapy

BACKGROUND AND PURPOSE:Breast cancer is the most common malignancy in women.Chemotherapy is one of the most important treatments for breast cancer.Clinically,TAC and AC-T are the most commonly chemotherapy regimens for breast cancer patients,among which doxorubicin and docetaxel are two most important chemotherapy drugs.Docetaxel is a water-insoluble compound that needs to be dissolved with polyoxyethylene castor oil.This solvent can induce allergic reactions frequently.Dexamethasone can relieve this allergic reaction and inhibit chemotherapy-induced nausea and vomiting,are routinely used as auxiliary drugs for TAC and AC-T regimens.Dexamethasone itself also has many side effects,which may increase the risk of diabetes,hypertension,and hyperlipidemia in patients,increase the incidence of cardiovascular deaths,and it has been reported in the literature that dexamethasone may induce cancer cells to chemotherapy drugs resistance,reduce the efficacy of chemotherapy.At present,the impact of dexamethasone on chemotherapeutic drugs doxorubicin and docetaxel forbreast cancer is still inconclusive.The present study is aimed to study the effect of dexamethasone on the efficacy of doxorubicin and docetaxel in breast cancer patients with TAC or AC-T regimen chemotherapy.METHODS:Cell proliferation rate of breast cancer cells MDA-MB-231 and MCF-7 was detected by Cell counting kit-8(CCK-8).Cell apoptosis was detected by flow cytometry and Hoechst staining.Real-time fluorescence quantification PCR and Western blot were used to detect the expression of Bcl-2 family related genes and proteins after different concentrations of dexamethasone and doxorubicin were applied to breast cancer cells.Transwell assay was used to detect migratory and invasive capabilities after the MDA-MB-231 cells were treated with dexamethasone.RESULT:1.Effect of dexamethasone alone on breast cancer cells MDA-MB-231 and MCF-7Compared with the control group,dexamethasone alone had no significant effect on the proliferation of MDA-MB-231 and MCF-7 breast cancer cells(p>0.05);compared with the control group,after being treated with 1 umol/L dexamethasone for 48 hours,the migration and invasion of the cells significantly decreased(p<0.05).Western blot tested the expression of MMP-9,a migration-related protein,decreased.2.Effect of dexamethasone and docetaxel on proliferation andapoptosis of MDA-MB-231 and MCF-7 breast cancer cellsCompared with the docetaxel group,CCK-8 assay found that dexamethasone with docetaxel did not significantly inhibit the proliferation of docetaxel(p>0.05);Compared with docetaxel alone,dexamethasone in combination with docetaxel increased the apoptotic rate of breast cancer cells slightly,but there was no statistical difference(p>0.05),which suggests that there was no significant effect of dexamethasone on docetaxel chemotherapy on breast cancer cells.3.Effect of dexamethasone and doxorubicin on cell proliferation and apoptosis of MDA-MB-231 and MCF-7 breast cancer cellsCompared with single doxorubicin group,CCK-8 assay found that the proliferation rate of MDA-MB-231 and MCF-7 cells in the combination of dexamethasone and doxorubicin groups increased significantly(P<0.05).The apoptosis rate of MDA-MB-231 cells treated with dexamethasone and doxorubicin for 48 h was(14.40±0.67)%,which was significantly lower than that of doxorubicin alone(22.53±1.12)%(P<0.05).The apoptosis rate of dexamethasone combined with doxorubicin in MCF-7 cells after treatment for 48 h was(15.05±1.41)%,which was significantly lower than that of doxorubicin alone(19.02±0.89)%(P<0.05).It was shown that the combination of dexamethasone and doxorubicin inhibited the chemotherapy effect of doxorubicin on breast cancer.Western blot showed that dexamethasone combined with doxorubicincould increase the expression of apoptosis-related genes and protein Bcl-2,and reduce the expression of Bax and Cleaved caspase-9,indicating that dexamethasone may be mediated through inhibition of Bcl-2 pathway on mitochondrial membrane,which reduces the apoptosis effect of doxorubicin on cancer cells.CONCLUSION:The use of dexamethasone in breast cancer chemotherapy can significantly inhibit the inhibition of proliferation and apoptosis induced by doxorubicin in breast cancer cells,but it does not affect the effect of docetaxel on breast cancer cells,indicating that dexamethasone in combination doxorubicin inhibits the efficacy of doxorubicin chemotherapy for breast cancer.The results suggest that the use of dexamethasone in clinical TAC chemotherapy for breast cancer may reduce the efficacy of chemotherapy,but dexamethasone is not combined with doxorubicin in the AC-T chemotherapy regimen,suggesting that the AC-T chemotherapy regimen may work better in clinical breast cancer chemotherapy.