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China Journal of Chinese Materia Medica ; (24): 2739-2743, 2014.
Article in Chinese | WPRIM | ID: wpr-299863

ABSTRACT

<p><b>OBJECTIVE</b>To study the apoptosis inducing effects of bufalin on various human osteosarcoma cells and the concerning molecular mechanisms.</p><p><b>METHOD</b>MTT assay was used to detect the growth inhibition rates of osteosarcoma cells U-20S, U-20S/MTX300, SaOS-2, IOR/OS9 treated with bufalin in different concentrations and times. The apoptosis of cells was observed flow cytometry 48 h following bufalin treatment. The proteomic techniques were used to separate and compare the treated and control groups 48 h after bufalin-incubation. Then, the proteomic results were validated by western blot.</p><p><b>RESULT</b>Bufalin inhibited the growth of human osteosarcoma cells U20S, U20S/MTX300 (methotrexate resistant cells), SAOS2, IOR/OS9 in a dose- and time-dependent manner. The 72 h IC50 were (37.43 +/- 4.1), (32.24 +/- 5.3) nmol x L(-1) in U20S,U20S/MTX300 cells,respectivly. Flow cytometry showed that the apoptosis cells were increased following bufalin treatment. The protein expression profile showed 24 differentiated expression proteins. Among these proteins, the level of an anti-apoptotic protein, heat shock protein 27 (Hsp27) decreased significantly and the result was then validated by western blot. Ectopic expression of Hsp27 could reduce the bufalin-induced apoptosis remarkably in U20S and U20S/MTX300 cells.</p><p><b>CONCLUSION</b>Bufalin could inhibit the cell growth and induce apoptosis on human osteosarcoma cells. The effect of bufalin may be related to the joint intervention with multiple protein targets. Among them, downregulation of Hsp27 plays a critical role in the bufalin-induced apoptosis in human osteosarcoma cells.</p>


Subject(s)
Humans , Antineoplastic Agents , Pharmacology , Apoptosis , Bufanolides , Pharmacology , Cell Line, Tumor , Cell Proliferation , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Gene Expression Regulation, Neoplastic , Osteosarcoma , Pathology , Proteomics
2.
Chinese Medical Journal ; (24): 1205-1208, 2011.
Article in English | WPRIM | ID: wpr-239866

ABSTRACT

<p><b>BACKGROUND</b>The coagulation function in carcinoma patients is abnormal, but in renal cell carcinoma the extent and relationships of coagulation function remain unclear. This study retrospectively investigated the relationships between coagulation function, clinical stage and metastasis in patients with renal cell carcinoma.</p><p><b>METHODS</b>A total of 350 consecutive patients admitted to our Urology Department from 2004 to 2010 were diagnosed with renal cell carcinoma by histopathologic examination and were included in this study. A total of 231 cases of renal benign tumors were considered as the control group. Fibrinogen, prothrombin time, activated partial thromboplastin time and international normalized ratio were evaluated in all subjects. Tumor size, clinical stage, lymph node metastasis, and distant metastasis were evaluated using radiologic imaging, intraoperative findings, and histological studies.</p><p><b>RESULTS</b>The preoperative plasma fibrinogen levels of patients with renal cell carcinoma ((383.9 ± 146.7) mg/dl) were significantly higher than those of the control group ((316.7 ± 62.0) mg/dl) (P < 0.01). We divided the renal cell carcinoma group into stages Ia, Ib, II, III, and IV. The fibrinogen values were (315.6 ± 64.6) mg/dl, (358.3 ± 91.1) mg/dl, (465.6 ± 164.7) mg/dl, (500.0 ± 202.1) mg/dl, and (585.8 ± 179.7) mg/dl, respectively. There were no significant differences in fibrinogen values between stage Ia and control groups. However, results of other stages showed significant differences when compared to control group values (P < 0.01). Using the cutoff value of 440 mg/dl, which defines hyperfibrinogenemia, plasma fibrinogen levels had a positive predictive value of 39.8% and a negative predictive value of 93.3% for predicting distant metastasis, with a sensitivity of 64.7% and specificity of 83.3%.</p><p><b>CONCLUSIONS</b>Preoperative plasma fibrinogen levels are elevated in patients with renal cell carcinoma with distant metastasis or lymph node metastasis. Potential metastasis is more likely if the tumor size larger than 4 cm. Increased preoperative plasma fibrinogen levels, especially hyperfibrinogenemia, may be an indicator of metastasis.</p>


Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Blood Coagulation , Physiology , Carcinoma, Renal Cell , Metabolism , Pathology , Fibrinogen , Metabolism , Kidney Neoplasms , Metabolism , Pathology , Lymphatic Metastasis , Neoplasm Metastasis , Neoplasm Staging , Retrospective Studies , Thromboplastin , Metabolism
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