Effects Of Dexamethasone On Breast Cancer MDA-MB-231Cells Sensitivity To Chemotherapy And Its Mechanism

Background: A large number of domestic and international epidemiologicalsurveys found that mental and psychological factors have a certain role in thedevelopment of malignant tumors, mainly by activating hypothalamic-pituitary-adrenal（HPA） axis and through releasing high doses of glucocorticoids exerting biologicaleffects, including the reduction of chemotherapy sensitivity and the increasedangiogenic capacity. Animal experiments had proved that if the mice grows in thestressful environment, the expression VEGF was significantly elevated in the tumortissue[1]. VEGF not only can promote angiogenesis of tumor, but also may regulate theexpression of Bcl-2which can anti-apoptosis, and have related to platinum resistance.Breast cancer is the most common malignant tumor in women. In recently years, itsincidence is obviously rising. Clinical observation found that mental and psychologicalfactors can reduce chemotherapy in patients with breast cancer, and shorten survivaltime[2].We analyze the reduction of chemotherapy efficacy in breast cancer may berelated to the activation of the HPA axis and glucocorticoids coursed by psychologicalfactors. Dexamethasone is the classic alternative medicine of glucocorticoids.Bydetecting the chemotherapy sensitive and testing the expression of VEGF in breastcancer cells after interference with dexamethasone in vitro, We designed to analysis theinfluence of dexamethasone on breast cancer cells and to provide certain theory basisfor the reduction of chemotherapy in patients with breast cancer coursed by mental andpsychological factors.Objective:To verify the chemotherapy sensitivity to cisplatin and the expressionof VEGF in breast cancer MDA-MB-231cells after intervening with dexamethasone.Methods: Using MTT to determinant the suppression of breast cancerMDA-MB-231cells which intervened with dexamethasone, cisplatin and dexamethasone combined with cisplatin respectively, calculating the median inhibitoryrate (IC₅₀) and drug combination index （CI） to analysis breast cancer cellschemotherapy sensitivity to cisplatin. Using immunocytochemical to detect theexpression of VEGF in breast cancer MDA-MB-231cells. Using SPSS17.0software tostatistic the experimental results with independent sample t test and one-way ANOVA,chi-square test. P <0.05for the difference means statistically significant.Results: Results of MTT show that:1.1.2x10^-3 mol/L concentration ofdexamethasone obviously restrained the growth rate of breast cancer MDA-MB-231cells, but the doses between1.2x10^-4mol/L to1.2x10^-8mol/L concentration ofdexamethasone had no inhibition or proliferation to breast cancer cells.2. Differentconcentrations of cisplatin obviously inhabited the survival of breast cancerMDA-MB-231cells, related with concentration and time, and the IC₅₀ of24h,48hwere9.0mg/L,7.5mg/L respectively.3. The combination effect of1.2x10^-7mol/Lconcentration of dexamethasone and cisplatin, IC₅₀ of cisplatin was8.3mg/L.Combination index （CI） was1.11.4. Among the groups of combination treatment,intervening with dexamethasone first reduces the chemotherapy sensitivity to cisplatinmost, and the differences had statistical significance （P <0.05）.Results of immunocytochemistry showed that the positive rate of VEGF in the testgroup was86.47%, had differences with the other group76.23%（P=0.025）.Conclusion:1. High dose of dexamethasone can inhibit the growth rate of breastcancer cells; Small dose of dexamethasone have no obvious effect ion to breast cancercells.2. Cisplatin have proliferate inhibition effect ion on MDA-MB-231cells and relatewith concentration and time.3. Dexamethasone can antagonist breast cancer cells chemotherapy sensitivity tocisplatin. The earlier intervention with dexamethasone, breast cancer cellschemotherapy sensitivity to cisplatin reduced more.4. After intervention with dexamethasone, the expression of VEGF in breastcancer MDA-MB-231cells were significantly increased, may be one reasons of thereduction of breast cancer cells chemotherapy sensitivity to cisplatin after interveningwith dexamethasone.