Hepatocyte growth factor ( HGF),a multifunctional cytokine,plays a biological role through acting on the cell surface transmembrane receptor c-Met.The growth,invasion and metastasis of many tumors are associated with the abnormalities of HGF-c-Met signaling pathway.Studies found that HGF and its receptor c-Met have close relations with the occurrence,metastasis,invasion and prognosis of multiple myeloma.

OBJECTIVETo explore the mechanism of matrine (Mat) induced human erythroleukemia TF-1 cell apoptosis and its effect on SALL4 expression.

METHODDifferent concentrations of the Mat (0.5, 1.0, 1.5, 2.0 g x L(-1) ) were cultured in vitro in TF-1 cells at different time (24, 48, 72 h). Cell proliferation was assayed by MTT. Cell cycle was determined by flow cytometry (FCM). Cell apoptosis was detected by Annexin V and PI double staining method. SALL4 mRNA expression was detected by reverse transcription RT-PCR (RTT-PCR).

RESULTAdministrated with Mat (0.5-2.0 g x L(-1)) after 24, 48, 72 h, the proliferation of TF-1 cells were inhibited (P < 0.01) , and in dose- and time-dependent manner. Half inhibitory concentration (IC50 ) was 1.0 g L(-1) at 48 h. After 48 h that the Mat acted on TF-1 cells, the proportion of G0/G1 phase cells increased while compared with the control group, and S phase cells decreased (P < 0.01). Apoptosis were 8.6% , 11.21%, 15.26% , 17.63%, which showed statistically significant difference (P < 0.01) compared with the control group (5.05%). RT-PCR results showed the ratio between SALL4 mRNA expression and beta-actin (internal reference) expression significantly decreased (P < 0.01) with Mat dose increased.

CONCLUSIONIn a certain range of concentration and time, Mat can inhibit TFT-1 cells proliferation. The mechanism is to make the cells G0/G1 phase blocked, to inhibit SALL4 gene expression and induce cell apoptosis.

Alkaloids ; pharmacology ; Antineoplastic Agents, Phytogenic ; pharmacology ; Apoptosis ; drug effects ; Cell Cycle ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Gene Expression ; drug effects ; Humans ; Leukemia, Erythroblastic, Acute ; drug therapy ; genetics ; metabolism ; physiopathology ; Quinolizines ; pharmacology ; Transcription Factors ; genetics ; metabolism

Objective: To compare the clinical value of FibroScan, FIB-4, APRI and AAR diagnosing hepatic fibrosis in chronic hepatitis B virus (HBV) carriers. Methods: A total of 213 patients with chronic HBV carriers diagnosed by clinical and liver biopsy were selected. And according to HBeAg status, 149 patients were divided into HBeAg-positive group and 64 patients were divided into HBeAg-negative group. The liver stiffness measurements (LSM) was measured by FibroScan (FS), FIB-4, APRI and AAR values were calculated using FIB-4, APRI and AAR formula. And all patients underwent liver biopsy in the same period. According to the degree of hepatic fibrosis in Knodell, one decision point was set: significant hepatic fibrosis (S ≥ 2). The Spearman correlation analysis method was used to analyze the correlation of indicators and the area under receiver operator characteristic curves (AUROCs) of LSM, FIB-4, APRI and AAR were drawn according to liver biopsy pathology results as gold standard. The value of LSM, FIB-4, APRI and AAR diagnosing hepatic fibrosis in chronic HBV carriers was retrospectively analyzed. Retrospective analysis of FS, FIB-4, APRI and AAR were divided into 149 HBeAg-positive chronic HBV carriers (HBeAg-positive group) and 64 HBeAg-negative chronic HBV carriers (HBeAg) in 213 patients with chronic HBV carriers and HBeAg Negative group) in the diagnosis of liver fibrosis. Results: The LSM of 213 patients with chronic HBV carriers, 149 patients with HBeAg-positive chronic HBV carriers and 64 patients with HBeAg-negative chronic HBV carriers were significantly correlated with liver fibrosis grade≥ 2 (P < 0.001). Regardless of HBeAg status, only LSM in the three groups had moderate evaluation efficacy for evaluating significant fibrosis(S≥2), and the positive predictive value was more than 94%, but the diagnostic accuracy was not high, the minimum was 46.31% (HBeAg-positive group), the maximum value of 67.19% (HBeAg-negative group), while the remaining three kinds of serum noninvasive liver fibrosis diagnostic model indicators and diagnostic efficacy are low. The LSM in the three groups showed a significant positive correlation with liver fibrosis grade (S)≥2. Conclusion LSM is more accurate than FIB-4, APRI and AAR in diagnosing chronic HBV carriers. Dynamically monitoring changes of LSM can earlier understand the progress of liver fibrosis than the three kinds of serology noninvasive diagnostic model and is contributed to the choice of liver biopsy timing.