Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The gene of buckwheat trypsin inhibitor (BTI) has been cloned and expressed in Escherichia coli. The yield of this recombinant inhibitor was over 12 mg/L by using one-step purification on a Ni2+-NTA Sepharose column. Its molecular weight was 9322.1 Da, determined by mass spectrum analysis. The MTT and cytometry analyses showed that recombinant BTI could specifically inhibit the proliferation of IM-9 human B lymphoblastoid cells (from patient with multiple myeloma) in a dose-dependent manner. The test of recombinant BTI-induced apoptosis in IM-9 cells implied that the inhibitor might have potential application in the treatment of cancer.
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PMID:Expression of a buckwheat trypsin inhibitor gene in Escherichia coli and its effect on multiple myeloma IM-9 cell proliferation. 1780 65

The aim of this study was to explore the mechanisms underlying effect of arsenic trioxide (As2O3) on myeloma cell line U266 in vitro. The viability and apoptosis of U266 cells were observed by MTT assay, flow cytometry and DNA agarose gel electrophoresis. The expression of hTERT mRNA was assessed by RT-PCR analysis. The variation of procaspase-3, bcl-2 and hTERT protein expression were detected by Western blot. The results indicated that the As2O3 could inhibit the growth of U266 cells significantly and the concentration of 50% growth inhibition (IC50) was 2 micromol/L. After treatment with 2.5 micromol/L As2O3 at 24, 48 and 72 hours, a dose- and time-dependent apoptosis of U266 cells could be observed. After treating U266 cells with 2 micromol/L As2O3 at different time points, a time-dependent reduction of procaspase-3, hTERT mRNA and protein was found without any change of bcl-2 expression. It is concluded that the As2O3 can change the mitochondrial transmembrane potential, initiating the mitochondial apoptosis pathway, leading in turn to caspase-3 activation, and inducing the apoptosis of U266 cells. These findings suggest that the reduction of hTERT plays a critical role in the apoptosis of U266 cells induced by As2O3.
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PMID:[Mechanisms underlying the effect of arsenic trioxide on proliferation inhibition and apoptosis induction in myeloma cell line u266]. 1795 74

The expression of vascular endothelial growth factor receptor 1(VEGFR-1) in human multiple myeloma KM3 cells in vitro, effects of valproic acid (VPA), as a histone deacetylase inhibitor, on cell proliferation and apoptosis and the underlying molecular mechanism were investigated. The effects of VPA on the growth of KM3 cells were studied by MTT assay. The apoptosis rate was determined with flow cytometry. The mRNA level of VEGFR was determined by RT-PCR; and immunocytochemistry was used to detect the protein level of ac-H4 and VEGFR. VPA inhibited proliferation of KM3 cells in a time- and dose-dependent manner. Treatment with VPA (4, 2, 1 and 0.5 mmol/L) for 48h, the apoptosis rates of KM3 cells were (13.27+/-3.54)%, (22.13+/-1.20)%, (24.41+/-2.23)% and(40.62+/-4.28)% respectively. The expression of VEGFR-1 in KM3 cells were decreased in VPA-treated group by the immunochemistry and RT-PCR, whereas the acetylated histone H4(ac-H4) accumulated. It suggested VPA could decrease the expression of VEGFR-1 in KM3 cells, and it might play an important role in regulating the proliferation and apoptosis of multiple myeloma cell line KM3 cells. These results provide the framework for clinical trials.
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PMID:Histone deacetylase inhibitor valproic acid inhibits proliferation and induces apoptosis in KM3 cells via downregulating VEGF receptor. 1806 35

The aim of this study was to investigate the effect of arsenic trioxide (As(2)O(3)) combined with bortezomib on the proliferation, apoptosis and beta-catenin level in myeloma cell lines. Myeloma cell lines RPMI8226, CZ-1 and NCI-H929 were treated with As(2)O(3) and bortezomib alone or in combination for 48 hours. Trypan blue dye exclusion and modified MTT were used to assess the cell viability. Flow cytometry with Annexin V-FITC and PI staining was used to detect the apoptosis rate. The beta-catenin level was analyzed by Western blot. The results showed that IC(50) of bortezomib to RPMI8226, CZ-1 and NCI-H929 were 46.9, 20.7 and 6.8 nmol/L, respectively. After the combination treatment with bortezomib (5 nmol/L) and As(2)O(3) (1 micromol/L), the cell viability of RPMI8226, CZ-1 and NCI-H929 decreased from 88.99%, 72.23%, 51.06% to 54.01%, 39.59%, 25.00%(p<0.05), the apoptosis rate increased from 11.1+/-0.1%, 26.8+/-1.7%, 46.8+/-5.5% to 36.1+/-2.2%, 60.4+/-3.8%, 76+/-5.6% (p<0.01) respectively. The Q value of two groups lies between enhancement and significant enhancement (1.198 - 3.75). Besides, beta-catenin levels in tested cell lines were decreased to 24.15%, 31.85%, 33.72% of their basic constitutions respectively (p<0.05). It is concluded that combination treatment of As(2)O(3) and bortezomib can enhance the proliferation inhibition and apoptosis induction of bortezomib to myeloma cell lines, reduce beta-catenin level, and increase the sensitivity of myeloma cell lines to bortezomib.
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PMID:[Effect of arsenic trioxide combined with bortezomib on proliferation, apoptosis and beta-catenin level in myeloma cell lines]. 1831 6

This study was aimed to investigate the effect of VEGF antisense RNA on proliferation and apoptosis in myeloma cell line U266 as well as on angiogenesis in endothelial cell ECV304, and to explore the feasibility of gene therapy for multiple myeloma using VEGF antisense RNA. The VEGF121 cDNA was inserted into multiple clone site of eukaryotic expression vector pIRES2-EGFP to construct the recombinant plasmid AS-VEGF. Restriction endonuclease analysis and DNA sequencing were used to confirm the reverse orientation of the VEGF cDNA. The recombinant plasmid was transfected into human myeloma cell line U266 and the positive clone was screened by G418. The VEGF mRNA and protein expressions of the positive clone were detected by RT-PCR and Western blot respectively. The viability and apoptosis of U266 cells were observed by MTT assay, flow cytometry. Angiogenesis was tested by network formation of endothelial cells on matrigel. The results indicated that the recombinant plasmid AS-VEGF expressing VEGF antisense RNA were constructed successfully. VEGF expression in U266 cells was blocked partially by VEGF antisense RNA. Expression of VEGF mRNA and protein decreased more significantly in U266 cells transfected by AS-VEGF than that in control group. Then increasing of apoptosis and inhibition of proliferation in U266 cells transfected by AS-VEGF were observed. Vasoformation on matrigel in the supernatants of U266 culture group transfected by AS-VEGF decreased more significantly than that in control group. It is concluded that VEGF antisense RNA can inhibit the expression of VEGF gene in U266 cells, thereby inhibits the proliferation of U266 cells; increases the apoptosis of U266 cells; and inhibits angiogenesis in vitro.
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PMID:[Effect of VEGF antisense RNA on inducing apoptosis of myeloma cells and inhibition of angiogenesis in endothelial cells in vitro]. 1842 55

The aim of this study was to explore the effect of arsenic trioxide (As(2)O(3)) on the methylation status of socs-1 gene in multiple myeloma cell lines U266, RPMI8226. The cell viability was assayed by MTT method. The methylation status of socs-1 gene was detected by methylation specific PCR. The expression of socs-1 gene mRNA was determined with real-time PCR. The cell apoptosis was analyzed by flow cytometry. The results indicated that hypermethylation of CpG island of socs-1 gene was observed without expression of socs-1 in myeloma cell lines U266, RPMI8226. The expression of socs-1 gene mRNA in each myeloma cell line increased significantly after exposure to As(2)O(3) for 72 hours as compared with the cell lines of wild type (p < 0.05). And cell proliferation was significantly inhibited, both early apoptosis and later apoptosis ratios increased in dose-dependent manner. It is concluded that As(2)O(3) may induce socs-1 demethylation and up-regulate the expression of the gene. This study provides a new thought and direction for exploring possible mechanism of cell apoptosis induced by As(2)O(3) and multiple myeloma treatment by As(2)O(3).
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PMID:[Arsenic trioxide induces socs-1 gene demethylation in myeloma cell lines]. 1892 96

Bisphosphonates consist of a family of pyrophosphate analogues that are currently being used to treat metastatic bone diseases as well as systemic bone diseases such as osteoporosis. There is accumulating evidence suggesting that patients treated with these bisphosphonates can develop, particularly with invasive dental procedures, osteonecrosis of the jaw. This present study investigated the ability of osteoblastic cells obtained from the alveolar bone of patients on long term intravenous bisphosphonate therapy to respond to agents normally involved in bone regulation and repair. The effects of platelet-derived growth factor-BB (PDGF-BB), 1,25-dihydroxycholecalciferol [1,25(OH)2VitaminD3] and parathyroid hormone (PTH) on basic parameters of cell viability, proliferation, and differentiation were studied. Osteoblastic cells from a diagnosed necrotic alveolar bone specimen obtained with consent from a multiple myeloma female patient, and a non-necrotic sample from a breast cancer female patient both on chronic bisphosphonate therapy (zolendronic acid) were successfully cultured. Cells from an alveolar bone specimen obtained from a female donor with no known medical conditions were also studied for comparative responses. The cells were exposed to 1,25(OH)2D3, PDGF, or PTH under various incubation conditions. The osteoblastic cell differentiation marker, alkaline phosphatase activity, was assayed using a biochemical analysis. Cell viability was assessed with an MTT assay which measures mitochondrial activity and cell proliferation with a tritiated thymidine assay. This study on osteoblastic cells grown from a necrotic alveolar bone from a multiple myeloma patient and a non-necrotic sample from a breast cancer patient, both on long term bisphosphonate treatment, suggests that viable cells from the bone are responsive to agents such as PTH, PDGF and 1,25(OH)2D3 with changes in alkaline phosphatase activity, proliferation and viability suggestive of normal osteoblastic cell responses observed in cultures from a donor of the same gender and age, but not on bisphosphonate treatment. This work provides a rationale for clinical studies to further assess whether the osteonecrosis that sometimes develops in patients treated with bisphosphonates, can be controlled or prevented by close attention to the levels of bone/calcium regulatory agents and/or, in some cases, therapeutic intervention with PDGF to restore regenerative processes that may be compromised at the necrotic site.
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PMID:Effects of platelet-derived growth factor, vitamin D and parathyroid hormone on osteoblasts derived from cancer patients on chronic bisphosphonate therapy. 1921 60

This study was aimed to investigate the effect of metabolic system in human hepatic cell microsome on antiangiogenic in vitro activity of thalidomide used in treating multiple myeloma and to explore the role of cytochrome CYP2C19. Human umbilical cord vein endothelial cells (hUCVECs) were treated with thalidomide alone or thalidomide co-incubated with human hepatic cell microsome. Cell proliferation ability was assessed by MTT assay, cell cycle analysis and detection of apoptosis were carried out by flow cytometry (FCM), migration activity of hUCVECs was determined by modified Boyden chamber and differentiation of hUCVECs was assayed by tube formation test. The results showed that thalidomide alone had no obvious direct effect on hUCVEC viability or apoptosis, mild effect on cell migration and no effect on tube formation. However, when co-incubated with human hepatic cell microsome, thalidomide significantly inhibited the hUCVECs viability. At 100 microg/ml, thalidomide co-incubated with human hepatic cell microsome, the proliferation ability of hUCVECs decreased by (11.7 +/- 3.9)%, apoptosis cells increased by 27.2%, the cell migration was down-regulated significantly, and the tube formation was obviously inhibited. When omeprazole, a specific inhibitor of cytochrome CYP2C19, was added into the co-incubation mixture, the effects of thalidomide on cell proliferation ability, apoptosis, migration and tube formation decreased. It is concluded that effect of human hepatic cell microsome is required for thalidomide's antiangiogenic activity in vitro and cytochrome CYP2C19 may be involved in the antiangiogenic effect of thalidomide.
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PMID:[Antiangiogenic activity of thalidomide in vitro mediated by cytochrome CYP2C19]. 1923 57

This study was purposed to investigate the effect of rapamycin on proliferation, apoptosis, cell cycle progression and the regulation of chemokine receptor CXCR4 on RPMI8226 cells. Different concentrations of rapamycin were used to treat the multiple myeloma cell line RPMI8226 for different times. The proliferation of the cells was detected by MTT assay; the apoptosis rate and cell cycle were determined by flow cytometry (FCM); apoptosis of cells was observed by inverted microscopy; the cylin D1, CXCR4 and mTOR mRNA expressions were detected by RT-PCR or FQ-PCR after treating RPMI8226 cells with different concentrations of rapamycin. The results indicated that the rapamycin could inhibit the proliferation of RPMI8226 cells and induce their apoptosis. The cell cycle was arrested at the G(0)/G(1) phase. PCR results showed the down-regulation of mTOR, cyclin D1 and mTOR mRNA expressions after treating RPMI8226 cells with different concentrations of rapamycin for 24 hours. It is concluded that the rapamycin significantly inhibits the growth of RPMI8226 cells in a dose-and time-dependent mannes and induce cell apoptosis. Cell cycle arrests at the G(0)/G(1) phase, may be due to the down-regulation of the mTOR and cyclin D1 expressions. In additions, the down-regulation of CXCR4 mRNA expression is correlated with the reduction of adhesion between myeloma cells and stromal cells.
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PMID:[Effect of rapamycin on proliferation, apoptosis and regulation of chemokine receptor CXCR4 in RPMI8226 cells]. 1937 72

The purpose of this study was to investigate the effect of thalidomide (THD) combined with dexamethasone (Dx) on multiple myeloma KM3 cells and its mechanism. The effect of the different concentrations and treatment time of THD or THD + Dx on KM3 cells was assayed by cytotoxicity test (MTT method), the inhibitory ratio of THD or THD + Dx on the KM3 cell growth was detected for choosing the best intervention condition. The expression levels of IL-6, TNF-alpha, VEGF, ES, survivin in supernatant of cells treated with best intervention condition were measured by indirect ELISA. The results indicated that an enhancement of cell growth inhibition was observed in treated KM3 cells along with increasing of drug concentrations and prolonging of treatment times, at the same time the THD combined with Dx could significantly inhibit the KM3 cell growth. The combination of THD in concentration of 80 or 100 microg/ml with Dx in concentration of 4 microg/ml decreased the expression of IL-6, TNF-alpha and survivin, increased the expression of ES, while no influence on VEGF expression was found. It is concluded that THD combined with Dx shows the synergistic inhibitory effect on KM3 cells, they bring the effect resistant to multiple myeloma probably through down-regulating the expression of IL-6, TNF-alpha and survivin, and up-regulating the expression of ES in KM3 cell.
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PMID:[Effect of thalidomide combined with dexamethasone on multiple myeloma KM3 cells]. 1969 26


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