[Effect of Matrine on cell cycle and human telomerase reverse transcriptase of human salivary adenoid cystic carcinoma].

OBJECTIVE: To investigate the effect of the traditional Chinese medicine Matrine on cell cycle and human telomerase reverse transcriptase (hTERT) of human ACC-M cell lines. METHODS: Different concentrations of Matrine were used in the medium of ACC-M cells. Change of cell cycle were detected by flow cytometry after ACC-M cell were cultivated with different concentrations Matrine (0.25, 0.50, 0.75, 1.00 mg x mL(-1)). Expression of hTERT was investigated by reverse transcription-polymerase chain reaction (RT-PCR) and indirect immunofluorescene and flow cytometry quantitative analysis. RESULTS: Matrine caused obviously the GdG1 phase block and inhibited proliferation of ACC-M cells. At same time, this effect was positive correlation to Matrine concentration and treat time. Matrine can inhibit the expression of hTERT mRNA and protein. CONCLUSION: Matrine can obviously inhibit cell cycle and down-regulate expression of hTERT. Inhibition of cell cycle is possible correlation with down-regulation expression of hTERT.

Vandetanib inhibits growth of adenoid cystic carcinoma in an orthotopic nude mouse model.

PURPOSE: Adenoid cystic carcinoma (ACC) can often be controlled with surgery and postoperative adjuvant radiotherapy but is also characterized by late local recurrence and distant metastasis. No effective systemic therapeutic agents have been found to alter the natural history of ACC. Therefore, new therapeutic approaches are needed. In this study, we evaluated whether vandetanib (Zactima), a potent inhibitor of vascular endothelial growth factor receptor-2 (VEGFR-2) and epidermal growth factor receptor (EGFR) tyrosine kinases, had antitumor efficacy in vitro and in an orthotopic nude mouse model of human ACC. EXPERIMENTAL DESIGN: The in vitro effects of vandetanib were assessed in three ACC cell lines on cell growth, apoptosis, and VEGFR-2 and EGFR phosphorylation levels. The in vivo antitumor activity of vandetanib was examined in nude mice bearing parotid gland ACC tumors. The mice were treated for 4 weeks with vandetanib (50 mg/kg/d) or placebo (control). Tumors were resected at necropsy, and immunohistochemical and immunofluorescence staining were done. RESULTS: In vitro, vandetanib caused dose-dependent inhibition of VEGFR-2 and EGFR phosphorylation in ACC cells. Vandetanib also inhibited the cell proliferation and induced their dose-dependent apoptosis. In vivo, mice in the vandetanib group had tumor volumes significantly lower than those in the control group (P < 0.01). In addition, immunohistochemical staining showed a decrease in microvessel density and an increase in apoptosis of both tumor cells and endothelial cells within the tumor xenografts. CONCLUSION: These results suggest that vandetanib inhibits the growth of ACC in vitro and in vivo, making it a promising novel agent for the treatment of ACC.

[Modulation of Chinese prescription Shenyang on Th1/Th2 cytokines in serum of SD rats with squamous cell carcinoma of the tongue].

PURPOSE: Prospective research demonstrated that Chinese prescription Shenyang could prolong the survival time and improve the survival rate of patients with oral squamous cell carcinoma (SCC). But the mechanism was not clear. The purpose of this study was to investigate effect of Shenyang on the level of Th1/Th2 cytokines in serum of SD rats with SCC of tongue and clarify its mechanism. METHODS: Among 80 SD rats fed by 0.002% 4-nitroquinoline-1-oxide (4NQO) drinking water for 36 weeks, 61 with SCC of tongue had been found and randomly divided into 4 groups, namely Shenyang A, Shenyang B, positive and negative control group. Before and after high and low dosage of Shenyang, acanthopanax senticoside and water had been given for 15 days respectively, peripheral blood serum was collected. Secretion of Th1-type cytokines, such as IFN-gamma, IL-2, TNF-alpha and Th2-type cytokines, such as IL-4, IL-10 were detected by enzyme-linked immunosorbent assay (ELISA). Statistical analysis was made with paired t test. RESULTS: Shenyang significantly enhanced ,the serum levels of Th1-type cytokine, TNF-alpha and IL-2 (P<0.05), and decreased the expression of Th2-type cytokine, IL-4 and IL-10(P<0.05). Serum IFN-gamma had been increased to some extent. CONCLUSION: Reversing Th2 to Th1 cytokines and then enhancing the immunity may be one of the mechanisms in anti-tumor effect of Shenyang. Supported by Science and Technology Development Fund (No.014319359) of Shanghai Municipality.

[Modulation of Chinese regimen granules of Shenyang on peripheral blood lymphocyte subsets of SD rats with SCC of tongue].

OBJECTIVE: Prospective research demonstrated that Chinese regimen granules of Shenyang could prolong survival time and improve survival rate of patients with oral squamous cell carcinoma (SCC). But the mechanism was not clear. The purpose of this study was to investigate Shenyang's effect on peripheral blood lymphocyte subsets of SD rats with SCC of tongue and explore immunological mechanism. METHODS: Among 80 SD rats fed by 0.002% 4-nitroquinoline-1-oxide (4NQO) drinking water for 36 weeks, 61 rats with SCC of tongue had been found and were randomly divided into 4 groups, namely Shenyang A, Shenyang B, positive and blank control groups. Before and after high and normal dosage of Shenyang, acanthopanax senticoside and water had been given for 15 days respectively, peripheral blood lymphocyte subsets were detected with flow cytometry. The data were statistically analyzed with paired t Test. RESULTS: Percentage of CD3+ CD4+ T cell and CD3-CD161a+ NK cell, ratio of CD4+/CD8+ were increased. Percentage of CD3+CD8+ T cell was decreased, and the effect was better than that of acanthopanax senticoside in improving the percentage of CD3-CD161a+ NK cell. CONCLUSION: Among anti-tumor mechanisms of Shenyang it is that corrects disorder of lymphocyte subsets and increases percentage of CD3-CD161a+ NK cell.