Long non-coding RNA HOTAIR modulates c-KIT expression through sponging miR-193a in acute myeloid leukemia.

HOTAIR is significantly overexpressed in various cancers and facilitates tumor invasion and metastasis. However, whether HOTAIR plays oncogenic roles in acute myeloid leukemia (AML) is still unknown. Here, we report that HOTAIR expression was obviously increased in leukemic cell lines and primary AML blasts. Clinically, AML patients with higher HOTAIR predicted worse clinical outcome compared with those with lower HOTAIR. Importantly, HOTAIR knockdown by small hairpin RNA inhibited cell growth, induced apoptosis, and decreased number of colony formation. Finally, HOTAIR modulated c-KIT expression by competitively binding miR-193a. Collectively, our data suggest that HOTAIR plays an important oncogenic role in AML and might serve as a marker for AML prognosis and a potential target for therapeutic intervention.

Methylated alteration of SHP1 complements mutation of JAK2 tyrosine kinase in patients with myeloproliferative neoplasm.

SHP1 negatively regulates the Janus kinase 2/signal transducer and activator of transcription (JAK2/STAT) signaling pathway, which is constitutively activated in myeloproliferative neoplasms (MPNs) and leukemia. Promoter hypermethylation resulting in epigenetic inactivation of SHP1 has been reported in myelomas, leukemias and other cancers. However, whether SHP1 hypermethylation occurs in MPNs, especially in Chinese patients, has remained unclear. Here, we report that aberrant hypermethylation of SHP1 was observed in several leukemic cell lines and bone marrow mononuclear cells from MPN patients. About 51 of 118 (43.2%) MPN patients including 23 of 50 (46%) polycythaemia vera patients, 20 of 50 (40%) essential thrombocythaemia and 8 of 18 (44.4%) idiopathic myelofibrosis showed hypermethylation by methylation-specific polymerase chain reaction. However, SHP1 methylation was not measured in 20 healthy volunteers. Hypermethylation of SHP1 was found in MPN patients with both positive (34/81, 42%) and negative (17/37, 45.9%) JAK2V617F mutation. The levels of SHP1 mRNA were significantly lower in hypermethylated samples than unmethylated samples, suggesting SHP1 may be epigenetically inactivated in MPN patients. Furthermore, treatment with 5-aza-2'-deoxycytidine (AZA) in K562 cells showing hypermethylation of SHP1 led to progressive demethylation of SHP1, with consequently increased reexpression of SHP1. Meanwhile, phosphorylated JAK2 and STAT3 were progressively reduced. Finally, AZA increased the expression of SHP1 in primary MPN cells with hypermethylation of SHP1. Therefore, our data suggest that epigenetic inactivation of SHP1 contributes to the constitutive activation of JAK2/STAT signaling. Restoration of SHP1 expression by AZA may contribute to clinical treatment for MPN patients.

Analysis of differentially expressed lncRNAs in differentiation of bone marrow stem cells into neural cells.

Many studies have reported micro RNAs involved in the differentiation of bone marrow mesenchymal stem cells (BMSCs) into neural cells; however, the roles of long non-coding RNAs (lncRNAs) in the differentiation of BMSCs into neural cells remain poorly understood. We used microarray assays to compare the lncRNA and messenger RNA (mRNA) expression profiles in BMSCs and neural-induced BMSCs. We found a total of 24 lncRNAs and 738 mRNAs that were upregulated and 32 lncRNAs and 682 mRNAs that were downregulated in samples induced for 3h; 27 lncRNAs and 864 mRNAs that were upregulated and 37 lncRNAs and 968 mRNAs that were downregulated in 6h samples; and 23 lncRNAs and 1159 mRNAs that were upregulated or downregulated in both the 3h and 6h samples. For 23 differentially lncRNAs and 83 differentially mRNAs, 256 matched lncRNA-mRNA pairs were found. GO (Gene ontology) analysis showed that these lncRNAs were associated with biological processes, cellular components, and molecular functions. Twenty-five pathways were identified by pathway analysis. Then, RT-qPCR validation of the differentially expressed H19, Esco2, Pcdhb18, and RGD1560277 genes confirmed the microarray data. Our study revealed the expression patterns of lncRNAs in the differentiation of BMSCs into neural cells, and many lncRNAs were differentially expressed in induced BMSCs, suggesting that they may play key roles in processes of differentiation. Our findings may promote the use of BMSCs to treat neurodegenerative diseases and trauma.

Epigenetic deregulated miR-375 contributes to the constitutive activation of JAK2/STAT signaling in myeloproliferative neoplasm.

Constitutive activation of Janus kinase 2/signal transducers and activators of transcription (JAK2/STAT) signaling caused by JAK2V617F and other mutations is central to the pathogenesis of myeloproliferative neoplasm (MPN). Negative regulators such as suppressors of cytokine signaling (SOCS) inhibit activated JAK2/STAT signaling. However, whether silencing of negative regulators facilitates JAK2/STAT signaling is unclear. Here, we report that loss of miR-375 expression contributes to the constitutive activation of JAK2/STAT signaling. MiR-375 reduced JAK2 protein level and repressed the activity of a luciferase reporter by binding 3'-untranslated regions, which was abolished by the mutation of the predicted miR-375-binding site. Meanwhile, a significant inverse correlation between the expressions of miR-375 and JAK2 was found in multiple types of leukemic cell lines and bone marrow mononuclear cells from MPN patients, suggesting that JAK2 may be a miR-375 target gene. Furthermore, forced expression of miR-375 inhibited constitutive and inducible JAK2/STAT signaling, suppressed cell proliferation, and decreased colony formation in hematopoietic progenitors from MPN patients. Finally, histone deacetylation (HDAC) inhibitors restored miR-375 expression, which was much lower in patients with MPN compared with healthy volunteers. Collectively, our data suggest that the loss of miR-375 expression enhances the constitutive and persistent activation of JAK2/STAT signaling. Restoration of miR-375 expression might contribute to the clinical treatment for MPN patients.

Honokiol induces cell cycle arrest and apoptosis via inhibiting class I histone deacetylases in acute myeloid leukemia.

Honokiol, a constituent of Magnolia officinalis, has been reported to possess potent anti-cancer activity through targeting multiple signaling pathways in numerous malignancies including acute myeloid leukemia (AML). However, the underlying mechanisms remain to be defined. Here, we report that honokiol effectively decreased enzyme activity of histone deacetylases (HDACs) and reduced the protein expression of class I HDACs in leukemic cells. Moreover, treatment with proteasome inhibitor MG132 prevented honokiol-induced degradation of class I HDACs. Importantly, honokiol increased the levels of p21/waf1 and Bax via triggering acetylation of histone in the regions of p21/waf1 and Bax promoter. Honokiol induced apoptosis, decreased activity of HDACs, and significantly inhibited the clonogenic activity of hematopoietic progenitors in bone marrow mononuclear cells from patients with AML. However, honokiol did not decrease the activity of HDACs and induce apoptosis in normal hematopoietic progenitors from unbilicial cord blood. Finally, honokiol dramatically reduced tumorigenicity in a xenograft leukemia model. Collectively, our findings demonstrate that honokiol has anti-leukemia activity through inhibiting HDACs. Thus, being a relative non-toxic agent, honokiol may serve as a novel natural agent for cancer prevention and therapy in leukemia.

[Expression of musashi-2 gene in leukemia stem cells from acute myeloid leukemia patients].

This study was aimed to detect the expression of Musashi-2 (Msi2) in acute myeloid leukemia (AML) and investigate the relationship between Msi2 and other clinical parameters, especially CD34. A total RNA was extracted from bone marrow of newly diagnosed AML patietns. The Msi2 mRNA expression in newly diagnosed AML patients was detected with real-time fluorescence quantitative RT-PCR. The expression level of CD34 in above-menthioned patients was detected by flow cytometry (FCM). The relationship between the expression of Msi2 mRNA and clinical outcome in AML patients was analysed. The results showed that (1)the expression of Msi2 mRNA in newly diagnosed AML patients was much higher than that in healthy volunteers (P < 0.05) , especially in M1, M4 and M5 patients; (2)the expression level of Msi2 did not correlate with age, sex, white blood cell count of peripheral blood, AML1/ETO and PML/RARa fusion gene (P > 0.05); (3) Msi2 expression level in patients with CD34(+) cells was significantly higher than that in patients with CD34(-) cells (P < 0.05). It is concluded that the Msi2 mRNA expresses in leukamia stem cells, the high expression of Msi2 mRNA has been found in newly diagnosed AML patients, especially in M1, M4 and M5 patients, the high expression also has been observed in patients with CD34(+).

Protective effect of resveratrol against acute lung injury induced by lipopolysaccharide via inhibiting the myd88-dependent Toll-like receptor 4 signaling pathway.

Resveratrol, a polyphenol mainly present in grapes and red wine, demonstrated varied pharmacological activities. The protective effects of resveratrol on acute lung injury (ALI) induced by lipopolysaccharide (LPS) have remained elusive. The present study investigated whether the protective effect of resveratrol on ALI induced by LPS was via inhibiting the myeloid differentiation primary response gene (myd88)­dependent toll­like receptor (TLR)4 signaling pathway. Mice were pretreated with 5 or 45 mg/kg resveratrol for three days prior to bronchial perfusion with 25 mg/kg LPS. At 12 h after surgery, the ratio of the wet to the dry (w/d) lung was calculated to assess tissue edema. Histological changes of the lungs were detected using hematoxylin and eosin staining and the protein expression levels of TLR4, myd88 and nuclear factor kappa­light­chain­enhancer of activated B cells (NF­κB) were measured by western blot analysis. The concentration of interleukin (IL)­6 and cyclooxygenase (COX)­2 in the bronchoalveolar lavage fluid were detected by ELISA. The results showed that resveratrol can suppress the edema, inflammatory cell infiltration and alveolar structure damage of lungs in mice with ALI and decrease the lung w/d ratio. Additionally, resveratrol markedly decreased the expression of TLR4, myd88 and NF­κB and decreased the concentration of inflammatory cytokines, including IL­6 and COX­2. Therefore, it can be concluded that resveratrol has a protective effect against ALI induced by LPS, at least in part by inhibiting the myd88­dependent TLR4 signaling pathway. In conclusion, resveratrol pretreatment has a protective effect against LPS­induced ALI in mice, which indicates that resveratrol may serve as a potential therapeutic agent for treating ALI in the clinic.

Histone deacetylases inhibitor trichostatin A increases the expression of Dleu2/miR-15a/16-1 via HDAC3 in non-small cell lung cancer.

Histone deacetylases (HDACs) inhibitor is a promising new approach to the treatment of lung cancer therapy via inhibiting cell growth and inducing apoptosis. miR-15a and miR-16-1 are important tumor suppressors through modulating B cell lymphoma 2 (Bcl-2), Cyclin D1, D2, and others. However, whether HDACs inhibitor modulates the expression of miR-15a/16-1 in lung cancer is still unknown. The purpose of our study was to identify a new miRNA-mediated mechanism which plays an important role in the anti-cancer effects of HDACs inhibitor. We found HDACs inhibitors trichostatin A (TSA) and sodium butyrate upregulated the expression of miR-15a/16-1, residing in the host tumor suppressor Dleu2 gene, through increasing the histone acetylation in the region of Dleu2/miR-15a/16-1 promoter in lung cancer cells. Moreover, among class Ι HDACs subtypes, only knockdown of HDAC3 by specific siRNA increased the hyperacetylation of Dleu2/miR-15a/16-1 promoter region and finally resulted in the upregulation of miR-15a/16-1. Furthermore, overexpression of miR-15a/16-1, which were always deleted or downregulated in lung cancer cells, effectively suppressed cell growth and reduced colony formation. Finally, TSA reduced the expression of Bcl-2, an important survival protein in lung cancer cells, partly through upregulation of miR-15a/16-1. Therefore, this offers a therapeutic strategy that lung cancer patients who exhibit low level of miR-15a/16-1 or high activity of HDACs may benefit from HDACs inhibitor-based therapy.

Histone deacetylases inhibitor sodium butyrate inhibits JAK2/STAT signaling through upregulation of SOCS1 and SOCS3 mediated by HDAC8 inhibition in myeloproliferative neoplasms.

Constitutive activation of Janus kinase 2/signal transducers and activators of transcription (JAK2/STAT) signaling has an important role in the oncogenesis of myeloproliferative neoplasms (MPNs) and leukemia. Histone deacetylases (HDACs) inhibitors have been reported to possess anticancer activity through different mechanisms. However, whether HDACs inhibitors suppress JAK2/STAT signaling in MPNs is still unknown. In this study, we show that the HDAC inhibitor sodium butyrate (SB) inhibited JAK2/STAT signaling and increased the expression of suppressors of cytokine signaling 1 (SOCS1) and SOCS3, both of which are the potent feedback inhibitors of JAK2/STAT signaling. SB upregulated the expression of SOCS1 and SOCS3 by triggering the promoter-associated histone acetylation of SOCS1 and SOCS3 in K562 and HEL cell lines. Importantly, we found that upon knockdown of each class I HDACs, only knockdown of HDAC8 resulted in the increased expression of SOCS1 and SOCS3. Moreover, overexpression of SOCS1 and SOCS3 significantly inhibited cell growth and suppressed JAK2/STAT signaling in K562 and HEL cells. Furthermore, SB increased the transcript levels of SOCS1 and SOCS3 and inhibited the clonogenic activity of hematopoietic progenitors from patients with MPNs. Taken together, these data establish a new anticancer mechanism that SB inhibits JAK2/STAT signaling through HDAC8-mediated upregulation of SOCS1 and SOCS3. Thus, HDACs inhibitors may have therapeutic potential for the treatment of MPNs.

Prognostic power of abnormal cytogenetics for multiple myeloma: a multicenter study in China.

BACKGROUND: Chromosomal abnormalities have been shown to play an important prognostic role in multiple myeloma (MM). Interphase fluorescence in situ hybridization (i-FISH) has been much more effective to identify cytogenetic aberrations in MM than conventional cytogenetic technique (CC). To clearly determine the cytogenetic features of Chinese MM patients and identify their prognostic implications, we designed a multicenter study based on i-FISH including 672 patients from 52 hospitals in China. METHODS: All 672 patients were systematically screened for the following genomic aberrations: del(13q), IgH rearrangement, del(p53) and 1q21 amplifications. RESULTS: The analysis showed that the chromosomal changes were detected in 22.1% patients by CC and in 82.3% patients by i-FISH. The most common abnormalities by CC were chromosome 1 aberrations (48.4%), -13/13q- (37.6%), hyperdiploidy (36.6%), hypodiploidy (30.1%) and IgH rearrangements (23.7%). The most frequent abnormalities by FISH was del(13q), which was found in 60.4% patients, whereas IgH rearrangement, 1q21 amplification and p53 deletions were detected in 57.6%, 49.0% and 34.7% cases, respectively. By statistical analysis, -13/13q- by CC was associated with low level of platelet (P = 0.015), hyperdiploidy was associated with low level of serum albumin (P = 0.028), and IgH rearrangement by FISH was associated with high level of ß2 microglobulin (P = 0.019). Moreover, 1q21 amplification and del(p53) by FISH conferred a high incidence of progressive disease (PD) after initial therapy. Metaphase detection of IgH rearrangements and chromosome 1 aberrations concurrently was associated with a short progression free survival (PFS) (P = 0.036). No significant prognostic implications of other cytogenetic abnormalities were found associated with overall survival and PFS. CONCLUSIONS: Chinese MM patients had similar cytogenetic abnormalities compared with the previous reported studies. However, the prognostic significance of FISH aberrations were not clearly determined and further study is required.

Design, synthesis and multidrug resistance reversal activity evaluation of 8-oxocoptisine derivatives.

Fifteen derivatives of 8-oxocoptisine were prepared based on that 8-oxocoptisine showed potent reversing effect against human cancer cells charactering multidrug resistance (MDR). The derivatives were evaluated for their growth inhibition and effects on reversing P-gp-mediated MDR against MCF-7/AMD cells. 12, 13-dinitro-8-oxocoptisine (6c), the most potential candidate with weak growth inhibition, significantly increased the sensitivity of adriamycin (ADM) against MCF-7/ADM cells by 213-fold at 10 µM that was comparable to the reference compound verapamil. The preliminary structure-activity relationships (SARs) of these derivatives were discussed on the basis of the in vitro MDR reversal activities.

Pure curcumin decreases the expression of WT1 by upregulation of miR-15a and miR-16-1 in leukemic cells.

BACKGROUND: Pure curcumin has been reported to down-regulate the expression of WT1 in leukemic cells. However, the molecular mechanism underlying the down-regulation of WT1 by curcumin is not completely delineated. The purpose of this present study is to identify a new miRNA-mediated mechanism which plays an important role in the anti-proliferation effects of curcumin in leukemic cells. METHODS: K562 and HL-60 cells were treated with different concentrations of curcumin for 24 and 48 hours, the level of miR-15a/16-1 and WT1 were detected by qRT-PCR and Western blotting. WT1 expression and cell proliferation were detected by Western blotting and CCK-8, after curcumin treated-K562 and HL-60 cells were transfected with anti-miR-15a/16-1 oligonucleotides. RESULTS: We found that pure curcumin upregulated the expression of miR-15a/16-1 and downregulated the expression of WT1 in leukemic cells and primary acute myeloid leukemia (AML) cells. Overexpression of miR-15a/16-1 deduced the protein level of WT1 in leukemic cells, but downregulation of WT1 by siRNA-WT1 could not increase the expression of miR-15a/16-1 in leukemic cells. These results reveal that curcumin induced-upregulation of miR-15a/16-1 is an early event upstream to downregulation of WT1. Furthermore, anti-miR-15a/16-1 oligonucleotides (AMO) partly reversed the downregulation of WT1 induced by pure curcumin in leukemic cells and AMO promoted the growth of curcumin treated-K562 and HL-60 cells. CONCLUSION: Thus, these data suggest for the first time that pure curcumin downregulated the expression of WT1 partly by upregulating the expression of miR-15a/16-1 in leukemic cells. miR-15a/16-1 mediated WT1 downregulation plays an important role in the anti-proliferation effect of curcumin in leukemic cells.

Synthesis and biological evaluation of oleanolic acid derivatives as antitumor agents.

Derivatives of oleanolic acid were synthesized and evaluated in vitro for their growth inhibition against human hepatocellular carcinoma cell line (HepG2) and colon cancer cell line (Col-02). Several derivatives exhibited moderate-to-good inhibitory activity, with 3 displaying the most promising inhibition [GI50 = 1.75 µM (HepG2), 0.71 µM (Col-02)]. Structure-activity relationship analyses of these derivatives demonstrated that a 1-en-2-cyano-3-oxo in ring A and a nitro at C-17 were important in retention of the inhibition against HepG2 and Col-02 cells.

[Bacterial 16S rRNA genes and expression of IL-1ß, TNF-α and IgA in prostate tissues].

OBJECTIVE: To investigate the role of bacteria in the etiology of chronic prostatitis. METHODS: Complete prostate specimens were obtained at autopsy from 192 organ donors (aged 20 - 38 years old) during 2002 to 2008 who died of non-prostatic diseases. One tissue taken from the peripheral prostatic zone according to McNeal was divided into two pieces. One piece of tissue was taken for routine pathological examinations and immunohistochemical studies of interleukin (IL)-1ß, tumor necrosis factor-α (TNF-α) and IgA. Another one was taken for PCR assay to detect the bacterial 16S rRNA genes (16S rDNA). RESULTS: Of 192 prostate specimens, 64 (33.3%) had pathological changes of chronic prostatitis and 38 (19.8%) specimens was positive for bacterial 16S rDNA. Positive rates of 16S rDNA in chronic prostatitis and non-prostatitis specimens were 50.0% (32/64) and 4.6% (6/128) respectively (χ(2) = 55.185, P < 0.001). Expressions of IL-1ß, TNF-α and IgA in specimens of chronic prostatitis were significantly higher than those in non-prostatitis specimens (P < 0.001). A positive correlation could be found among three immunohistochemical indicators (P < 0.01). In 64 specimens with chronic prostatitis, a significant expression of IL-1ß, TNF-α and IgA was more often demonstrated in 16S rDNA positive group than in 16S rDNA negative group (P < 0.001). CONCLUSIONS: The up-regulations of bacterial 16S rDNA, cytokines and immunoglobulin A are involved in inflammatory response of chronic prostatitis. Bacterial infection may be an important cause of chronic prostatitis.

In vitro neural differentiation of bone marrow stromal cells induced by cocultured olfactory ensheathing cells.

Bone marrow stromal cells (BMSCs) could be induced to differentiate into neural cells under certain conditions, nevertheless, optimal protocols that could be reproducible and reliable in generating transplantable BMSCs in vitro are still not available. We studied for the first time the neural differentiation of BMSCs induced by coculturing with olfactory ensheathing cells (OECs). BMSCs and OECs were isolated from bone marrow and nasal olfactory lamina propria of adult SD rats respectively, then brought to coculture with transwell culture dishes. At various time points (0h, 6h, 12h, 24h, 72h, 1 week and 2 weeks post-coculture), BMSCs were morphologically observed and processed for immunofluorescence and reverse transcription-polymerase chain reaction (RT-PCR). The number of cells assuming neural morphology dramatically increased at 1- and 2-week-post-coculture, so as the number of immunoreactive cells labeled by neural markers NSE, beta-III-tubulin, MAP2, GFAP and p75(NTR). Our findings demonstrate that BMSCs can efficiently differentiate into neural cells when coculturing with OECs, and the present protocol provides an alternative neurogenesis pathway for generating sufficient numbers of neural cells from BMSCs.

[Investigation on occupational hazards of ultraviolet light, sunscreen awareness and behaviors in Wuhan city traffic police].

OBJECTIVE: To understand the awareness of occupational hazards to ultraviolet (UV) and sunscreen awareness, protective measures in Wuhan City traffic police on duty outside. METHODS: The investigation included questionnaire survey in Wuhan City 367 traffic police on duty outside, talk with them face to face, fill in the questionnaires, and medical examine skin of exposed parts of body of them and 134 Wuhan City administration staffs. RESULTS: They understand UV harm to the human body and skin well (94.8% of them know that UV harm to skin), did not understand sun skin care and protective measures enough, and did not adopt enough sun skin care and protective measures (only 3.8% of them use sun skin care more than twice); but contrast to older persons, younger traffic police had better understanding of UV radiation damage on the human body and the skin, and sunscreen products and protective measures, paid more attention to sunscreen, and had less chance of sunburn (in the past 5 years, 18.3% of younger traffic police had sunburnt more than 3 times, but for older traffic police, the number is 30.3%). Traffic police had more skin problems than administration staffs in exposed parts of body (Traffic police face appears oily and large pores, facial pigmentation spots, face telangiectasia, deep wrinkles crude rates respectively were 73.7%, 40.4%, 36.5%, 10.4%, but for administration staffs, the numbers respectively were 26.1%, 15.7%, 15.7%, 1.5%). CONCLUSION: UV can induce skin problems in exposed parts of body. The traffic police should be enhanced the publicity and education on UV-related knowledge and occupational hazards, especially for older traffic police.

Synthesis and characterization of new liver targeting 5-fluorouracil-cholic acid conjugates.

The objective of this work was to develop a liver-specific antihepato carcinoma agent. A series of 5-fluorouracil / cholic acid conjugates (5-FU-cholic acid conjugates) were prepared and tested for their chemical characteristics and bio-distribution properties. The in-vitro stability trial showed 5-FU-cholic acid conjugates could be completely hydrolyzed by heating at 70 degrees C in an acidic solution, pH = 1, for 5 min. The fast and complete hydrolysis of these compounds could be compatible with a fast separation and analysis method to shorten the analysis time. The decomposition speeds of the 5-FU-cholic acid conjugates in different organs of mice at several time points after oral administration were evaluated by measuring the concentrations of regenerated 5-FU in organ tissue. The results were compared with those of the controls, which was a group of mice orally taking 5-FU. The concentrations of 5-FU in mice liver tissue were remarkably increased after oral administration of the prodrugs, and were much larger than if only orally administered 5-FU. The results suggested the feasibility to improve therapeutic efficiency of liver targeting treatments by using cholic acid as the vector of drugs.

[Effects of matrine on the apoptosis and expression of adhesion molecule in multiple myeloma RMPI8226 cells].

To investigate the effects of matrine on apoptosis and expression of adhesion molecules in human multiple myeloma cell line RPMI8226 cells, RPMI8226 cells were incubated with indicated concentrations of matrine. The growth of RPMI8226 cells was observed by CCK-8 colorimetric assay and apoptosis was detected by flow cytometry using Annexin V-FITC/PI staining. The cell cycles were analyzed by PI staining. Flow cytometry using Annexin V-FITC/PI staining was used to detect the expression of cell adhesion molecules, including CD44, CD44v6, CD54 and CD106. The results showed that RPMI8226 cell viability in presence of matrine decreased markedly in a dose- and time-dependent manners. The apoptosis could be induced by matrine and its level increased following the augmentation of the drug concentration. After treated by matrine for 48 hours, a concentration-dependent increase of cells in G(0)/G(1) phase and a decrease in S phase could be detected, but no obvious change of cell count was found in G(2)/M phase. Treatment of RPMI8226 cells with matrine for 48 hours resulted in decrease of expression levels of CD44 and CD54, while expressions of CD44v6 and CD106 had no significant change. It is concluded that matrine induces in vitro apoptosis, suppresses proliferation in multiple myeloma cells and depresses expression of some adhesion molecules.