TBX3 knockdown suppresses the proliferation of hypopharyngeal carcinoma FaDu cells by inducing G1/S cell cycle arrest and apoptosis.

The T-box transcription factor family member TBX3 has been demonstrated to participate in the development of various types of cancer, including head and neck squamous cell carcinoma. However, little is currently known about its role in hypopharyngeal carcinoma. In the present study, the involvement of TBX3 in hypopharyngeal carcinoma was investigated. Immunohistochemical assays revealed that TBX3 levels were increased in hypopharyngeal carcinoma compared with normal tissue samples, accompanied by upregulated N-cadherin and downregulated E-cadherin. Lentivirus-mediated TBX3 knockdown efficiently suppressed its expression and inhibited the proliferation of FaDu cells. The opposite was observed in TBX3-overexpressing FaDu cells. These results indicate that TBX3 is essential for FaDu cell proliferation. Furthermore, TBX3 silencing led to a disturbance of the cell cycle, leading to a decrease in the G1 phase and an increase in the S phase. In addition, apoptosis was enhanced following TBX3 knockdown. The present results suggest TBX3 as a potential therapeutic target in hypopharyngeal carcinoma.

In vitro and in vivo superior radiosensitizing effect of berbamine for head and neck squamous cell carcinoma.

BACKGROUND: Berbamine (BBM), one of the bis-benzylisoquinoline products isolated from Berberis amurensis, has been demonstrated for its anticancer effect against leukemia, breast cancer, liver cancer, etc. There are some studies focusing on the chemosensitization effect of BBM. However, there is no report about whether BBM could enhance the anticancer effect of radiation, which made us to explore the possible radiosensitization effect of BBM. MATERIALS AND METHODS: Here, in vitro cytotoxicity of BBM was evaluated on two kinds of head and neck squamous cancer cell lines. Clonogenic assay was performed to study the radiosensitization effect of BBM. Western blot was utilized to elucidate the possible mechanism underlying the radiosensitization effect. RESULTS: BBM effectively inhibited the growth of two kinds of cancer cells in a time- and dose-dependent manner. Radiation plus BBM led to significantly more reduction of the colony-forming ability of cancer cells when compared with radiation alone. BBM plus radiation led to the most reduction of STAT3 phosphorylation, followed by the significant decrease of the ratio of Bax/Bcl-2. In vivo study demonstrated that the combinational administration of BBM and radiation generated the most significant tumor-delaying effect among all of the treatment regimens. CONCLUSION: We reported, in the current study, the potential role of BBM in not only treating cancer by itself but also offering a promising way to improve the efficacy of radiotherapy by inhibiting the activation of STAT3 and subsequently inducing the apoptosis of cancer.

Association of TBX2 and P21 expression with clinicopathological features and survival of laryngeal squamous cell carcinoma.

BACKGROUND: The expression of P21 and TBX2 in laryngeal squamous cell carcinoma (LSCC) and their corresponding adjacent normal laryngeal tissues, as well as their association with clinical pathological features and survival remain unclear. METHOD: we used the RT-PCR and immunohistochemistry to detect their mRNA and protein levels in 75 LSCC patients. We also use log-rank test and Cox models to compare survival among different groups. RESULTS: The mRNA expression level of TBX2 was up-regulated, while P21 was down-regulated in LSCC compared with their matched adjacent laryngeal tissues (All P < 0.001). The expression of P21 was correlated with tumor stage, lymph node metastasis and smoking; and TBX2 expression was associated with lymph node metastasis, differentiation degree and smoking (All P < 0.05). Patients with high TBX2 and low P21 expression had significantly worse survival than those with low TBX2 and high P21 expression, respectively (All P < 0.05). A significant correlation between expression of TBX2 and P21 (Pearson, P < 0.05) was observed. Furthermore, multivariable analysis showed that patients with low TBX2 and high P21 expression alone had a significantly reduced risk for overall death compared with those with low TBX2 and high P21 expression. The risk for overall death was even lower for patients with both low and high expression of both genes than any other co-expression status of both genes (HR, 0.1; 95% CI, 0.0-0.9). CONCLUSION: These results suggest that abnormal expression of P21 and TBX2 in tumors may jointly, or individually, predict poor prognosis of LSCC.

Hsa-miR-34c suppresses growth and invasion of human laryngeal carcinoma cells via targeting c-Met.

MicroRNAs (miRNAs) are small noncoding RNA molecules that negatively modulate gene expression at the post-transcriptional level. A growing number of studies has shown that more and more miRNAs are aberrantly expressed and involved in the pathogenesis of several types of cancers. Here, we report that the down-regulated hsa-miR-34c was also involved in oncogenesis of laryngeal carcinoma. Our studies indicated that hsa-miR-34c functioned as a tumor suppressor which inhibited growth and invasion of human laryngeal carcinoma cells. Furthermore, in our study, an inverse relationship between the expression of hsa-miR-34c and c-Met was identified in 10 paired fresh samples from tumor tissues and adjacent normal tissues. Infection of hsa-miR-34c mediated by lentivirus suppressed the expression of c-Met directly. In addition, introduction of c-Met cDNA lacking 3'-UTR largely abrogated hsa-miR-34c-induced cell growth and invasion inhibition. These findings suggest aberrantly down-regulated hsa-miR-34c is a critical factor that contributes to malignancy in human laryngeal carcinoma by a mechanism involving targeting of c-Met.

[Effect of jieminqufeng decoction on cyclic nucleotides from the rats of allergic rhinitis].

OBJECTIVE: To observe the curative effect of Jieminqufeng decoction to the rats of allergic rhinitis and study the mechanism by which it treats allergic rhinitis. METHOD: Forty wistar rats were divided into 4 groups at random. There are Jieminqufeng decoction group, cetirizine group, model control group and normal control group. The rats of allergic rhinitis were established with ovalbumin. We surveyed the behavioral changes of rats, searched eosinophilic granulocytes in the nasal secretion, detected the contents of cAMP and cGMP in the blood plasma and nasal mucosa. RESULT: The model control group had typical symptoms of allergic rhinitis and the eosinophilic granulocytes could be found more frequently. The contents of cAMP and cAMP/cGMP rose in the blood plasma and nasal mucosa (P < 0.01). However, the changes of jieminqufeng decoction group were small. CONCLUSION: The jieminqufeng decoction is an effective drug to allergic rhinitis. Its possible mechanism is that it changes the contents of cAMP and cGMP, lessens inflammatory reaction and blocks up the allergy.