Nucleolar and spindle­associated protein 1 promotes non­small cell lung cancer progression and serves as an effector of myocyte enhancer factor 2D.

As a potential oncogene, nucleolar and spindle­associated protein 1 (NUSAP1) is involved in the regulation of tumor cell proliferation, metastasis and drug resistance. However, the role of NUSAP1 in non­small cell lung cancer (NSCLC) remains unclear. The present study aimed to investigate the biological function and underlying molecular mechanisms of NUSAP1 in NSCLC. NUSAP1 expression was measured in NSCLC tissues and cell lines via immunohistochemistry and western blotting, respectively. NSCLC cell lines stably inhibiting NUSAP1 were established to investigate its effects on cell proliferation, colony formation and invasion, and on in vivo tumorigenicity. Additionally, the upstream and downstream mechanisms of NUSAP1 in regulating NSCLC progression were investigated. The results indicated that NUSAP1 expression was upregulated in NSCLC tissues and cell lines. High NUSAP1 expression was associated with tumor size, TNM stage, lymph node metastasis and poor patient survival, whereas knockdown of NUSAP1 inhibited NSCLC cell proliferation, colony formation and invasion. Furthermore, downregulation of NUSAP1 decreased the growth of NSCLC xenografts in vivo. In addition, myocyte enhancer factor 2D (MEF2D) directly targeted the NUSAP1 promoter, thereby enhancing the mRNA and protein expression levels of NUSAP1. Moreover, the results demonstrated that MEF2D expression was upregulated in NSCLC tissues and was positively correlated with NUSAP1 expression. MEF2D­knockdown decreased NSCLC cell proliferation, colony formation and invasion. NUSAP1 upregulation reversed the effects of MEF2D­knockdown on NSCLC progression. Furthermore, it was observed that MEF2D­knockdown inhibited the accumulation and nuclear translocation of ß­catenin, thereby repressing the activation of the Wnt/ß­catenin signaling pathway in NSCLC cells, whereas NUSAP1 upregulation rescued the effects of MEF2D­knockdown on the activation of the Wnt/ß­catenin signaling pathway. In conclusion, the findings of the present study indicated that the MEF2D/NUSAP1 signaling pathway promoted NSCLC progression by inducing the activation of Wnt/ß­catenin signaling, and this novel mechanism may represent a potential treatment target for patients with NSCLC.

Molecular mechanisms of apoptosis in hepatocellular carcinoma cells induced by ethanol extracts of Solanum lyratum Thumb through the mitochondrial pathway.

AIM: To explore the induction effects and mechanism of Solanum lyratum Thumb (ST) on human hepatocellular carcinoma SMMC-7721 cells through the mitochondrial pathway. METHODS: The experiments were conducted on three groups: an experimental group (with ST ethanol extracts' concentration being 2.5, 5 and 10 mg/L), a negative control group (with only nutrient solution, 0 mg/L ST ethanol extracts), and a positive control group (2.5 mg/L DDP). The inhibition rate of cell proliferation was checked by using the methyl thiazolyl tetrazolium method, and cell apoptosis was tested by TUNEL method. Furthermore, RT-PCR was used to examine mRNA expression of Fas, FasL, caspase-8, caspase-3, p53 and Bcl-2 genes. RESULTS: Compared with the negative control group, the inhibition and apoptosis rates of the experimental group with different concentrations of ST extracts on human hepatocellular carcinoma SMMC-7721 cells significantly increased (P < 0.05). Besides, the mRNA expression of FasL and Bcl-2 significantly decreased (P < 0.05) while the mRNA expression of Fas, caspase-8, caspase-3 and p53 increased significantly. When compared with the positive control group, the experimental groups with 5 mg/L ST ethanol extracts showed effects similar to the positive control group. CONCLUSION: ST ethanol extracts induced the apoptosis of hepatocellular carcinoma SMMC-7721 cells through up-regulated Fas, caspase-8, caspse-3 and p53, and down-regulated FasL and Bcl-2 in the mitochondrial pathway.

[Apoptosis-inducing effect of Scutellaria barbata extract on human lung cancer SPC-A-1 cells and the expression of apoptosis associated genes].

OBJECTIVE: To explore the apoptosis-inducing effect of Scutellaria barbata extract (SBE) and the expression of apoptosis associated genes survivin and caspase-3 on human lung cancer SPC-A-1 cells. METHODS: Lung cancer SPC-A-1 cells were treated with 2.5, 5 and 10 mg/L for 48 h,and the cells were treated with 2.5 mg/L DDP as positive control. The inhibitory rat was evaluated by MTT assay. Apoptotic rate was determined by TUNEL method. The expression of survivin and caspase-3 mRNA were detected by semi-quantitive RT-PCR. RESULTS: Compared with control group, the inhibitory rate was increased obviously (P < 0.001), the apoptotic rate was increased markedly (P < 0.01), the expression of caspase-3 mRNA was increased significantly (P < 0.05 or P < 0.01), while survivin mRNA was decreased markedly (P < 0.05 or P < 0.01) in SBE groups. CONCLUSION: SBE can induce apoptosis of SPCA-1 cells. The molecular mechanism may be related to up-regulating expression of caspase-3 and down-regulating expression of survivin genes.