DJ-1 overexpression confers the multidrug resistance phenotype to SGC7901 cells by upregulating P-gp and Bcl-2.

Gastric cancer (GC) is one of the most malignant tumors with high incidence and mortality worldwide, and the multidrug resistance (MDR) often results in chemotherapy failure in GC. DJ-1 has been well indicated to be associated with drug resistance in multiple cancers. However, the role of DJ-1 in the MDR of gastric cancer cells and its possible mechanism remain to be elucidated. Therefore, the current study was investigated whether DJ-1 expression is differential in parental gastric cancer cell SGC7901 and vincristine (VCR)-induced gastric cancer MDR cell SGC7901/VCR, and whether DJ-1 plays a significant role in development of MDR in gastric cancer. The results showed that DJ-1 expression in SGC7901/VCR cells was significantly higher than its sensitive parental SGC7901 cells. Furthermore, DJ-1 overexpressed gastric cancer cell line SGC7901/LV-DJ-1 led to the increase of cell survival rate, the IC50 of chemotherapeutic drugs and number of cell clones as well as decrease of cell cycle G0/G1 phase ratio compared with its parental cells under the treatment of VCR, adriamycin (ADR), 5-Fluorouracil (5-FU) and cisplatin (DDP). However, the DJ-1 knockdown stable cell line SGC7901/VCR/shDJ-1 reversed the above mentioned series of MDR. Moreover, it was found that upregulation of DJ-1 protein expression promoted the pumping rate of GC cells to ADR and reduced the apoptotic index of GC cells treated with chemotherapeutic drugs by upregulating P-gp and Bcl-2. Similarly, knocking down DJ-1, P-gp or Bcl-2 displayed a converse effect. In conclusion, the current study demonstrated that DJ-1 overexpression confers the MDR phenotype to SGC7901 cells and this process is related to DJ-1 promoting active efflux of drugs and enhancing the anti-apoptotic ability of MDR GC cells by upregulating P-gp and Bcl-2.

Resveratrol attenuates myocardial hypoxia/reoxygenation-induced cell apoptosis through DJ-1-mediated SIRT1-p53 pathway.

Resveratrol, a multi-functional phytoalexin, has been well indicated to exert cardioprotective effects by weakening ischemia/reperfusion (I/R) injury, and cell apoptosis is a vital way in I/R injury. SIRT1-p53 pathway has strong significance in regulating cell apoptosis. DJ-1 can directly bind to SIRT1 and stimulate the activity of SIRT1-p53. Therefore, the current study was determined whether Resveratrol attenuates hypoxia/reoxygenation (H/R)-induced cell apoptosis, and whether DJ-1-mediated SIRT1 activation involves in the cardioprotective effects of Resveratrol. The results showed that remarkable decrease in the number of apoptotic cells along with reduction of lactate dehydrogenase release and restoration of cell viability emerged when Resveratrol was applied in the H9c2 cells exposed to H/R. Moreover, Resveratrol increased DJ-1 expression and promoted the interaction of DJ-1 with SIRT1, which further contributed to subsequent restoration of SIRT1 activity and decrease of acetylation level of p53. However, above cardioprotective effects of Resveratrol were abrogated by DJ-1 siRNA and SIRT1 specific inhibitor Sirtinol. In conclusion, the current study demonstrated that Resveratrol suppressed H/R-induced cell apoptosis, which may be conducted by up-regulating DJ-1, and later activating SIRT1 activity and subsequently inhibiting p53 acetylation level in the H9c2 cells.

[Analysis of Immunophenotypes in 329 Patients with B-ALL at Different Ages].

OBJECTIVE: To investigate the immunophenotypes of B cell acute lymphoblastic leukemia (B-ALL) in patients at different age and to explore its clinical application in prognosis prediction and individualized treatment. METHOD: The immunophenotyping in 329 patients with B-ALL at different ages was performed by CD45/SSC gate four-color fluorescence flow cytometry. RESULTS: In all patients detected the highest incidence of lymphoid-associated antigens was CD19, HLA-DR, CyCD79a and cTdT, followed by CD10, CD22, CD34, CD38, CD20 and CyIg. B-ALL showed a higher concomitant expression rate of myeloid antigens CD13 and CD33; the CD11b, CD15, CD117 and T antigens (CD4, CD7 and CD56) were rarely expressed. CD10⁻ pro-B acute lymphoblastic leukemia (Pro - B-ALL) was predo-minant in infantile group (60%) with CD117 higher expression (40%). Subtype Pro-B-ALL was rarely expressed in childhood and adolescent group, but the incidence of disease increased as the age increase, the incidence of youth group (22.7%) and middle-aged' group (14.8%) were significantly higher than childhood group (4.4%). The influence of age on immunophenotypic characteristics of the adult B-ALL was not significant, the heterogeneity of antigen expression was less in the adult patients at different ages. The expression of CD10 and CD38 was lower, while expression of CD34, CD13 and CD33 were higher in adult patients than those in children patients. There was no significant difference in incidence of precursor-B-ALL (Pre-B-ALL) among different age groups (P > 0.05), but its incidence increased along with age increasing, and the expression of CD20 was higher in Pre - B-ALL than that in Pro - B-ALL and common B-ALL. CONCLUSION: The immunophenotype characteristics of B-ALL in the patients at different ages is of great value in prediction for disease prognosis and guidence of individualized treatment.