Esomeprazole improves the acidic microenvironment of epithelial ovarian cancer by inhibiting the expression of VATPase

Purpose: To determine the effect of esomeprazole on apoptosis of ovarian cancer cells and their sensitivity to paclitaxel, and the underlying mechanism.Methods: Human ovarian paclitaxel-resistant cancer cells were cultured in vitro, and treated with esomeprazole at doses of 50, 100 and 250 mol/L. Cell proliferation was determined using MTT assay. Paclitaxel-resistant cells were divided into control group, esomeprazole group, paclitaxel group, and esomeprazole + taxol group. Western blot was employed for the assay of protein levels of bcl-2, Bcl-xl, P-gp and V-ATPase, while BCECF-AM method was employed to determine changes in intracellular pH.Results: Esomeprazole significantly inhibited the proliferation of paclitaxel-resistant cells in a dosedependent manner. The half-maximal inhibitory concentration (IC50) value of esomeprazole + paclitaxel was significantly low, when compared with those of the other treatments (p < 0.05). Apoptosis was significantly higher in esomeprazole + paclitaxel group than in any other treatment group (p < 0.05). The expressions of Bcl-2 and P-gp in esomeprazole + paclitaxel group decreased significantly, relative to the corresponding values for other groups, while protein expression of bcl-xl was markedly increased. The intracellular pH value of esomeprazole + paclitaxel group was significantly lower than those for other treatment groups (p < 0.05).Conclusion: Esomeprazole improves the acidic microenvironment of epithelial ovarian cancer by inhibiting the expression of V-ATPase, and restores the sensitivity of ovarian cancer cells to paclitaxel by inhibiting their proliferation and apoptosis. This revelation may explain patients’ resistance topaclitaxel. Keywords: Esomeprazole, V-ATPase, Apoptosis, Ovarian cancer, Taxol, Sensitivit

Propofol affects the biological behavior of ovarian cancer SKOV3 cells via ERK1/2-MMP-2/9 signaling pathway

Purpose: To investigate the effect of propofol on the biological behavior of ovarian cancer SKOV3 cells, and the mechanism of action involved. Methods: SKOV3 cells cultured in vitro were randomly divided into control group, fat emulsion group, low-dose propofol group (LDPG, 25 μmol/L), medium-dose propofol group (MDPG) (50 μmol/L) and high-dose propofol group (HDPG) (100 μmol/L). Apoptosis was determined by flow cytometry, while Transwell assay was used to measure the migration and invasion abilities of the cells. The protein levels of ERK1/2, MMP-2, MMP-9 were assayed with Western blotting. Moreover, the cells were transfected with siERK, and the regulatory effect of propofol on ERK1/2-MMP-2/9 signaling pathway was determined. Results: Apoptosis in HDPG was significantly reduced, relative to MDPG, while migration and invasion were enhanced, relative to MDPG (p < 0.05). Moreover, MMP-2, ERK1/2, and MMP-9 proteins were significantly higher in MDPG and HDPG than in control, fat emulsion and LDPGs (p < 0.05), and were upregulated in HDPGs, relative to MDPG (p < 0.05). In contrast, propofol did not up-regulate these proteins in siRNA-treated cells. Conclusion: Propofol enhances the migration, proliferation, and invasive ability SKOV3 cells, and upregulates the expressions of MMP-2, ERK1/2, and MMP-9 in these cells, via a mechanism related to the activation of ERK1/2-MMP-2/9 signaling route. These properties provide novel leads for the development of new drugs for ovarian cancer Keywords: Propofol, ERK1/2-MMP-2/9 signal route, Ovarian cancer, Biological behavio

Clinical correlates of autoimmune thyroiditis and non-autoimmune hypothyroidism in treatment-naive patients with major depressive disorders

Background: Thyroid autoimmunity is a potentially critical factor that is often neglected in the association be-tween subclinical hypothyroidism (SCH) and depressive disorders. This study aimed to investigate the clinical correlates of autoimmune thyroiditis (AIT) and non-autoimmune hypothyroidism (NAIH) in treatment-naive patients with major depressive disorder (MDD). Method: Using a cross-sectional design, we recruited a total of 1718 outpatients with treatment-naive MDD. Demographic and relevant clinical information including duration of MDD, severity of depression and anxiety, psychotic symptoms, suicide attempts, thyroid function parameters, etc. were collected. According to thyroid function parameters, patients were classified as AIT, NAIH, latent Hashimoto&#39;s thyroiditis (LH) and euthyroidism (ET). Results: Patients with SCH (including AIT and NAIH) had older age at onset, and were more likely to have psychotic symptoms compared to those with ET. Multiple linear regression analysis showed that SCH was associated with duration of MDD and HAMD scores. Logistic regression analysis showed that the odds of having more severe anxiety and metabolic syndrome were greater among patients with SCH compared to those with ET. The odds of having suicide attempts were greater among patients with AIT than among those with ET. Limitation: Because of the cross-sectional design of this study, we were unable to sort out causality between MDD and SCH. Conclusion: Our findings suggested that AIT and NAIH were associated with duration of MDD, HAMD scores, severity of anxiety, and metabolic syndrome. However, only AIT in SCH was associated with suicide attempts.</p

Clinical correlates of autoimmune thyroiditis and non-autoimmune hypothyroidism in treatment-naive patients with major depressive disorders

Background: Thyroid autoimmunity is a potentially critical factor that is often neglected in the association be-tween subclinical hypothyroidism (SCH) and depressive disorders. This study aimed to investigate the clinical correlates of autoimmune thyroiditis (AIT) and non-autoimmune hypothyroidism (NAIH) in treatment-naive patients with major depressive disorder (MDD). Method: Using a cross-sectional design, we recruited a total of 1718 outpatients with treatment-naive MDD. Demographic and relevant clinical information including duration of MDD, severity of depression and anxiety, psychotic symptoms, suicide attempts, thyroid function parameters, etc. were collected. According to thyroid function parameters, patients were classified as AIT, NAIH, latent Hashimoto's thyroiditis (LH) and euthyroidism (ET). Results: Patients with SCH (including AIT and NAIH) had older age at onset, and were more likely to have psychotic symptoms compared to those with ET. Multiple linear regression analysis showed that SCH was associated with duration of MDD and HAMD scores. Logistic regression analysis showed that the odds of having more severe anxiety and metabolic syndrome were greater among patients with SCH compared to those with ET. The odds of having suicide attempts were greater among patients with AIT than among those with ET. Limitation: Because of the cross-sectional design of this study, we were unable to sort out causality between MDD and SCH. Conclusion: Our findings suggested that AIT and NAIH were associated with duration of MDD, HAMD scores, severity of anxiety, and metabolic syndrome. However, only AIT in SCH was associated with suicide attempts