SRF-miR­29b-MMP2 axis inhibits NSCLC invasion and metastasis.

MicroRNAs play key roles in tumour metastasis. miR­29b was previously reported to act as a tumour suppressor or an oncogene in diverse cancers. However, its accurate function and mechanism in metastasis of no-small cell lung cancer (NSCLC) are not well known. In this study, we describe the function of miR­29b in NSCLC metastasis and its regulatory mechanisms. We found that miR­29b is downregulated in high-metastatic NSCLC cells and low-expression of miR­29b in primary NSCLC tissue was correlated with lymph node metastasis. Both gain- and loss-of-function study indicated overexpression of miR­29b could suppress migration and invasion abilities of high-metastatic NSCLC cells, while downregulation of miR­29b expression promoted migration and invasion of low-metastatic NSCLC cells in vitro. Moreover, introduction of miR­29b inhibited high­metastatic NSCLC cells, in vivo, metastasis to liver and lungs. Mechanistically, miR­29b, induced by the transcription factor SRF, posttranscriptionally downregulates MMP2 expression by directly targeting its 3'-untranslated regions. These findings indicate a new regulatory mode, whereby miR­29b, which is inhibited by its upstream transcription factor SRF, was able to promote its direct target MMP2 leading to NSCLC invasion and metastasis.

[Study on effect of heavy metal cadmium ions on the ultramicrostructure damage of Pheretima aspergillum gastrointestinal epithelial cells].

OBJECTIVE: To study the effect of cadmium ions of different concentrations on gastrointestinal epithelial cells structure of Pheretima aspegillum (PA). METHODS: PA were contaminated with cadmium ions of different concentrations,and the structure of the body skin was observed, under light microscope and transmission electron microscope. RESULTS: With the increasing of cadmium ions concentration, a large number of lysosomal hyperplasia could be seen in the PA intestinal epithelial cells, the Golgi complex distributed around, and some Golgi complex hyperplasiaed, extended to a large bubble, microvilli, cilia arranged in irregular, disordered. While in the group contaminated with the high concentration cadmium ions, such as 30 mg/kg, the microvilli of the PA intestinal epithelial cells contracted, necrotic ulcer lesions occurred in the ciliated cells. CONCLUSION: The ultrastructure damage extent of PA gastrointestinal epithelial cells is dependent on the amount of the heavy metal contamination. PA with lower concentration Cd contamination shows mainly lysosomal proliferation, indicating heavy metal accumulation in lysosomes to eliminate toxic substances as a responsible reaction, this kind of damage is reversible. However, PA with higher concentration Cd contamination shows mainly microvilli and mitochondrial damage, nuclear membrane disintegration, nucleoplasm spillover, leading to necrosis, irreversible damage, indicating heavy metal accumulation of PA is related to this trait of intestinal epithelial cells.

[Effects of VEGF-A/VEGF-C antisense oligodeoxynucleotide on angiogenesis, lymphangiogenesis, and tumor growth of breast cancer].

BACKGROUND & OBJECTIVE: Angiogenesis and lymphangiogenesis are closely related to tumor metastasis. Vascular endothelial growth factor-A (VEGF-A) is considered as an important factor in promoting angiogenesisû while VEGF-C is the most critical factor in VEGF family in promoting lymphangiogenesis, and exerts synergistic effect with VEGF-A in angiogenesis. This study was to investigate the effects of VEGF-A/VEGF-C antisense oligodeoxynucleotide (ASODN) on the angiogenesis, lymphangiogenesis, and tumor growth of breast cancer. METHODS: VEGF-A/VEGF-C ASODN was constructed and injected into orthotopic transplantation tumor model of human breast cancer in athymic mice. Tumor growth was observed. The expression of VEGF-A and VEGF-C was detected by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry. Microvessel density (MVD) and lymphatic microvessel density (LMVD) were measured by enzymohistochemistry. RESULTS: Tumor formation time was significantly longer and tumor weight was significantly lower in ASODN group than in control group [(13.00+/-2.83) days vs. (7.67+/-1.63) days, P<0.05û (0.45+/-0.14) g vs. (0.92+/-0.37) g, P<0.05]. The inhibition rate of tumor growth was 51.09% in ASODN group. The mRNA and protein expression of VEGF-A and VEGF-C were significantly weaker in ASODN group than in control group (P<0.05) The MVD and LMVD was significantly lower in ASODN group than in control group (21.83+/-2.86 vs. 41.33+/-4.03, 18.67+/-4.67 vs. 31.83+/-2.33, P<0.05). CONCLUSION: VEGF-A/VEGF-C ASODN could inhibit angiogenesis and lymphangiogenesis in breast cancer, and further inhibit tumor growth and metastasis.

[Expression of vascular endothelial growth factor A and C in human breast cancer and their significance].

BACKGROUND & OBJECTIVE: Vascular endothelial growth factor (VEGF) family is related to angiogenesis. VEGF-A and VEGF-C are closely related to tumorigenesis and lymphatic metastasis. This study was to detect the expression of VEGF-A and VEGF-C in breast cancer, and explore their correlation to cell proliferation, microvessel density (MVD), and lymphatic metastasis of breast cancer. METHODS: The expression of VEGF-A, VEGF-C, proliferating cell nuclear antigen (PCNA), and CD34 in 98 samples of breast cancer were detected by SP immunohistochemistry. RESULTS: The positive rate of VEGF-A was 85.7%; that of VEGF-C was 90.8%. The positive rates of VEGF-A and VEGF-C were significantly higher in cancers with lymph node metastasis than in cancers without lymph node metastasis (P<0.05). The positive rate of PCNA was 98.0%; its expression level was increased with the expression levels of VEGF-A and VEGF-C (r=0.432, P=0.000; r=0.294, P=0.001). MVD was significantly higher in cancers with lymph node metastasis than in cancers without lymph node metastasis(64.26+/-26.40 vs. 50.29+/-29.35, P<0.05). MVD was positively correlated to the expression of VEGF-A (r=0.327, P<0.001), but had no correlation to VEGF-C (r=0.123, P>0.05). CONCLUSIONS: VEGF-A mainly mediates angiogenesis, cell proliferation, and metastasis of human breast cancer. VEGF-C promotes cell proliferation of human breast cancer; it is correlated to lymph node metastasis, but has no correlation to MVD.

Statins initiated after hypertrophy inhibit oxidative stress and prevent heart failure in rats with aortic stenosis.

OBJECTIVE: Heart failure is a major and escalating public health problem. Recent studies have demonstrated that statins prevented chronic heart failure (CHF) in animal studies. However, it is unknown whether statins therapy initiated after left ventricular (LV) hypertrophy is evident can still effectively prevent CHF. This study tested the hypothesis that statins can prevent the transition of hypertrophy to heart failure. METHODS AND RESULTS: The rats were studied at 6, 12, and 20 weeks after aortic stenosis (AS) operation. Some rats were given simvastatin (2.0 mg kg(-1) per day) from 13 weeks after AS operation for 8 weeks. Coarctation of aorta in rats resulted in compensatory LV hypertrophy (LVH), concomitant with an increase of superoxide levels and cardiomyocyte apoptosis in LV tissues at 12 weeks after AS operation. This was followed by CHF with a progressive increase in superoxide levels and cardiomyocyte apoptosis in LV tissues at 20 weeks after AS operation. Simvastatin treatment initiated from 13 weeks after AS operation significantly improved LV function and reduced superoxide levels and cardiomyocyte apoptosis in LV tissues. Pretreatment of simvastatin suppressed the hydrogen peroxide-induced apoptosis of cultured cardiomyocytes from neonatal rats. CONCLUSIONS: These data indicate that long-term administration of simvastatin improved LV function and prevented the transition of hypertrophy to CHF. Inhibition of oxidative stress and cardiomyocyte apoptosis may contribute to the benefits of simvastatin treatment on heart of rats with AS.