ABSTRACT
Aim To explore the cytotoxic and synergistic effects of decitabine and ruxolitinib on HEL cells with TET2 knockdown. Methods Stable TET2 knockdown by shRNA was established in HEL cell line. The change of cell proliferation was measured by CCK-8 assay. The median lethal dose (IC50) and colony formation assay were used to evaluate the cytotoxic effects of decitabine and ruxolitinib, the synergistic effects of which was further analyzed by Chou-Talalay method. Results The inhibition of TET2 increased the proliferative capacity of HEL cells. HEL cell lines became resistant to decitabine following shRNA-media- ted TET2 inactivation. Colony formation assay showed that the drug sensitivity of decitabine and ruxolitinib both decreased in TET2 knockdown HEL cells. The synergistic inhibitory effects of ruxolitinib and decitabine on TET2 knockdown HEL cells were observed. Conclusion The combination of ruxolitinib and decitabine may be an effective therapeutic strategy for accelerated or blast phase MPN patients with JAK2V6m and TET2 mutations.
ABSTRACT
Polycythemia vera is a clonal malignant hematopoietic disorder that results from genetic alterations in hematopoietic stem cells, which is characterized by two or three-line blood cells increase, and mainly by erythrocytosis. This article reviews research situation of PV in China, including pathogenesis, clinical features, disease progression and therapeutic options, which helps clinical specialists to carry out precise diagnosis and treatment.
ABSTRACT
The different types of Ph-negative myeloproliferative neoplasm(MPN) possess the same JAK2V617 F mutation. JAK2 inhibitor, ruxolitinib, is only valid in some of MPN, which indicates JAK2 target is not the only molecular pathway of MPN. Epigenetic genes mutations, including TET2 and ASXL1, are involved in the progression and transformation of MPN. In addition, avoiding thromboembolism and reducing the risk of transformation into acute leukemia(AL) or myelofibrosis(MF) still is the therapeutic goal of polycythemia vera(PV) and essential thrombocytosis(ET). The goal of treatment in primary myelofibrosis(PMF) is to improve the quality of life and prolong the survival of patients. For the patients with PMF, stratification based on the efficacy of ruxolitinib and profound genetic detection is a reasonable supplement to the existing of stratification of clinical risk.
ABSTRACT
This study was designed to investigate the effect of 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glycoside(TSG)on hypoxia/reoxygenation(H/R)-induced oxidative stress injury and its potential mechanism in human bronchial epithelial cell(BEAS-2B)cells. BEAS-2B cells were exposed to H/R treatment. Level of intracellular ROS was detected using DCFH-DA probe and fluorescence microplate reader. Production of MDA and activity of SOD were evaluated with MDA and SOD kits. Nucleus was shaped by DAPI staining. Translocation of Bax to mitochondria was observed in MCF-7/GFP-Bax cells. Change in mitochondrial membrane potential was detected by JC-1 staining. Release of cytochrome C from mitochondria was detected by immunofluorescence. Expressions of mitochondrial/cytoplasmic Bax and cytochrome C, caspase-9, caspase-3, phosphorylated MAPK, HIF-1α and phosphorylated p53(p-p53)were determined by Western blotting. TSG significantly improved cell viability and reduced H/R-induced ROS production in BEAS-2B cells, while significantly decreased MDA production. It inhibited Bax translocation and nucleus fracture, reversed the decrease in mitochondrial membrane potential and inhibited the release of cytochrome C and following activation of caspase-9/caspase-3. Simultaneously, TSG down-regulated the signals of SAPK JNK1/2 and p38 MAPK without an impact in ERK1/2. It attenuated expression of HIF-1α and phosphorylation of p53. This study suggests that TSG could protect BEAS-2B against H/R-induced apoptosis, perhaps through the MAPK, HIF-1α and p53 pathways.