Objective To investigate the synergistic effects of Herceptin and 9-cis-RA on the proliferation, cell cycle and apoptosis of HER2-positive breast cancer cells. Methods MDA-MB-453 breast cancer cells were treated with 5 ?g/ml Herceptin or 1 ?mol/L 9-cis-RA or both for 24, 48 or 72 h. The proliferation of MDA-MB-453 breast cancer cells was determined by MTT, the pro-apoptotic effects were detected by TUNEL, the cell cycle phase was detected by FCM. Results As compared with control group, Herceptin and 9-cis-RA synergistically inhibited the proliferation of MDA-MB-453 breast cancer cells, and the percentage of G_ 0 /G_ 1 cells increased after treatment with Herceptin and 9-cis-RA for 72 h. Simultaneously, Herceptin and 9-cis-RA synergistically induced the apoptosis of MDA-MB-453 cells. Conclusion Herceptin and 9-cis-RA could synergistically and effectively inhibit MDA-MB-453 breast cancer cells by blocking their cell cycle progression and inducing their apoptosis.

BACKGROUNDThere are limited eligible clinical markers at present to monitor the progress of chronic myeloid leukemia (CML). Heme oxygenase-1 (HO-1), as one of the most important oxidation-regulating enzymes in vivo, suggests the onset and progression of cancer when highly expressed. Furthermore, HO-1 level is related with the occurrence and development of hematological diseases. But the relationship between HO-1 expression and progression/relapse of CML has seldom been studied hitherto. This study aimed to investigate the relationship between them to find out a new molecular marker for prediction.

METHODSA total of 60 peripheral blood and bone marrow (BM) samples from 25 CML patients in different phases were collected respectively to detect the expressions of HO-1 and bcr/abl using real-time PCR. Routine blood test was performed to detect the changes of leukocyte and platelet counts. The proportion of primitive cells in BM was detected by flow cytometry. The relationship between high HO-1 expression and CML progression and relapse was explored by the analysis of variance by Wilcoxon test and linear regression analysis. The diagnostic accuracy and cutoff values were determined by receiver operating characteristic curve.

RESULTSRelative expression of HO-1 mRNA in CML patients peripheral blood was significantly higher than that of donors (P < 0.0001), which were 0.57±3.78 and (1.417±1.125)×10(-6), respectively. HO-1 expression level in CML patients was 0.061 5±0.062 4, which decreased to 0.009 4±0.006 7 upon CMoR, and remained remarkably higher 0.016 3±0.017 5 than that of normal donors (1.417±1.125)×10(-6), P < 0.001. When relapse occurred, HO-1 expression significantly increased from 0.020 6±0.021 0 to 3.852±10.285 in CMoR stage and undergoing relapse. According to progression of CML, HO-1 expression level in CML patients increased from CP (0.009 5±0.017 6) to AP (0.028 0±0.055 7) and then to BP (0.276 7 ± 0.447 0). And there was a linear correlation between HO-1 expression and proportion of primitive CML cells. The diagnostic accuracies and cutoff values of HO-1 expression for CML-CP, CML-AP, and CML-BP were 1.0, 0.748, and 0.965, respectively, as well as 0.000 070, 0.001 917, and 0.020 696, respectively.

CONCLUSIONHO-1 may be a potential molecular indicator for the progression and relapse of CML.

Bone Marrow ; metabolism ; Female ; Flow Cytometry ; Gene Expression ; Heme Oxygenase-1 ; blood ; genetics ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; diagnosis ; enzymology ; pathology ; Male ; Predictive Value of Tests ; Real-Time Polymerase Chain Reaction