Scutellarin suppresses human colorectal cancer metastasis and angiogenesis by targeting ephrinb2.

Tumor induced angiogenesis is an attractive target for anti-cancer drug treatment. Scutellarin, which is a native compound derived from scutellaria altissima leaves, has already been proved to possess anti-tumor activities. Nevertheless, their effects in colorectal cancer metastasis and angiogenesis have not been evaluated. In order to reveal the anti-angiogenic and anti-metastasis capacity of scutellarin, wound healing and Transwell chamber inserts invasion were done in colorectal cancer cells, and cell proliferation as wells colony formation were conducted to identify the proliferation inhibition of colorectal cancer in vitro. The growth inhibition of scutellarin was further definite by a mouse colorectal xenograft model in vivo. Herein, we demonstrated scutellarin suppressed colorectal cancer cell viability and colony formation in vitro, and remarkably reduced tumor growth in vivo mouse xenografts. Additionally, scutellarin restrained colorectal cancer cells-induced angiogenesis, inhibited human umbilical vascular endothelial cells (HUVECs) migration, tube formation of HUVECs, and micro-vessel formation in chick embnyo chorioallantoic menbreme (CAM) assay. Altogether, our results exhibited the evidence that scutellarin inhibit colorectal cancer angiogenesis and metastasis via targeting ephrinb2 signaling, with the potential of an anti-tumor agent for cancer treatment.

Identification of ACTG2 functions as a promoter gene in hepatocellular carcinoma cells migration and tumor metastasis.

Metastatic hepatocellular carcinoma (HCC) remains a mostly incurable disease. The fact that the identity of the mechanisms that regulate metastasis in HCC is known hampers the development of anti-metastatic therapies. Currently, there is no effective treatment for HCC once it is progressed to metastatic stage. Therefore, further study to elucidate the molecular mechanism underlying the metastasis of HCC is urgently required for the improvement of HCC treatment. Here, we describes actin gamma smooth muscle 2 (ACTG2) over-express in HCC and demonstrates high-expression of ACTG2 as a promising therapeutic target in HCC metastasis. The use of shRNA to knock-down ACTG2 impaired cells migration and invasion in vitro. Moreover, silencing of ACTG2 causes almost complete inhibition of metastasis in vivo. In contrast, overexpression ACTG2 significantly enforces HCC cells migration and metastasis. Finally, ACTG2 boosts the metastatic potential of HCC cells in a Notch homolog 1 (Notch1) dependent manner. Collectively, our study reveals a critical role of ACTG2 in HCC tumor metastasis, and renders it a novel target for the treatment of HCC.

Effects of insulin-like growth factor 1 receptor and its inhibitor AG1024 on the progress of lung cancer.

The type 1 insulin-like growth factor receptor (IGF-1R) and its downstream signaling components have been increasingly recognized to drive the development of malignancies, including non-small cell lung cancer (NSCLC). This study aimed to investigate the effects of IGF-1R and its inhibitor, AG1024, on the progression of lung cancer. Tissue microarray and immunohistochemistry were employed to detect the expressions of IGF-1 and IGF-1R in NSCLC tissues (n=198). Western blotting was used to determine the expressions of IGF-1 and phosphorylated IGF-1R (p-IGF-1R) in A549 human lung carcinoma cells, and MTT assay to measure cell proliferation. Additionally, the expressions of IGF-1, p-IGF-1R and IGF-1R in a mouse model of lung cancer were detected by Western blotting and real-time fluorescence quantitative polymerase chain reaction (FQ-PCR), respectively. The results showed that IGF-1 and IGF-1R were overexpressed in NSCLC tissues. The expression levels of IGF-1 and p-IGF-1R were significantly increased in A549 cells treated with IGF-1 as compared to those treated with IGF-1+AG1024 or untreated cells. In the presence of IGF-1, the proliferation of A549 cells was significantly increased. The progression of lung cancer in mice treated with IGF-1 was significantly increased as compared to the group treated with IGF-1+AG1024 or the control group, with the same trend mirrored in IGF-1/p-IGF-1R/IGF-1R at the protein and/or mRNA levels. It was concluded that IGF-1 and IGF inhibitor AG1024 promotes lung cancer progression.

Estrogen receptorß2 regulates interlukin-12 receptorß2 expression via p38 mitogen-activated protein kinase signaling and inhibits non-small-cell lung cancer proliferation and invasion.

Lung cancer is one of the most common types of cancer and is the leading cause of cancer-related mortality worldwide. Estrogens are known to be involved in the development and progression of non-small-cell lung cancer (NSCLC). These effects are initially mediated through binding of estrogen to estrogen receptors (ERs), in particular ERß2. Our preliminary studies demonstrated that ERß2 and interleukin-12 receptorß2 (IL-12Rß2) expression are correlated in NSCLC. The present study investigated the expression of these proteins in NSCLC cells and how changes in their expression affected cell proliferation and invasion. In addition, it aimed to explore whether p38 mitogen-activated protein kinase (p38MAPK) is involved in the regulation of IL-12Rß2 expression by ERß2. An immunocytochemical array was used to observe the distribution of ERß2 and IL-12Rß2. Co-immuoprecipitation was employed to observe the interaction between p38MAPK and IL-12Rß2, by varying the expression of ERß2 and p38MAPK. Western-blot analysis and reverse transcription-polymerase chain reaction assays were used to investigate the mechanism underlying ERß2 regulation of IL-12Rß2 expression. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, scratch wound healing and Transwell assays were used to investigate the impact of ERß2 on proliferative, invasive and migratory abilities of NSCLC cells. ERß2 was predominantly found in the cytoplasm and nucleus, whilst IL-12Rß2 was largely confined to the cytoplasm, although a degree of expression was observed in the nucleus. Compared with normal bronchial epithelial cells, IL-12Rß2 and ERß2 were overexpressed in the NSCLC cell groups. Coimmuoprecipitation demonstrated an interaction between p38MAPK and IL-12Rß2. ERß2 appeared to upregulate IL-12Rß2 expression and inhibition of p38MAPK attenuated this effect. ERß2 and IL-12Rß2 expression inhibited the proliferation, metastasis and invasion of NSCLC cell lines, but knockout of IL-12Rß2, even in the presence of ERß2, led to an increase in NSCLC cell proliferation and invasiveness. In conclusion, to the best of our knowledge this study is the first to demonstrate that IL-12Rß2 may be important in the mechanisms underlying ERß2 inhibition of NSCLC development, and that this interaction may be mediated via p38MAPK.

PKM2 regulates hepatocellular carcinoma cell epithelial-mesenchymal transition and migration upon EGFR activation.

Pyruvate kinase isozyme type M2(PKM2) was first found in hepatocellular carcinoma(HCC), and its expression has been thought to correlate with prognosis. A large number of studies have demonstrated that epithelial-mesenchymal transition (EMT) is a crucial event in hepatocellular carcinoma (HCC) and associated metastasis, resulting in enhanced malignancy of HCC. However, the roles of PKM2 in HCC EMT and metastasis remain largely unknown. The present study aimed to determine the effects of PKM2 in EGF-induced HCC EMT and elucidate the molecular mechanisms in vitro. Our results showed that EGF promoted EMT in HCC cell lines as evidenced by altered morphology, expression of EMT-associated markers, and enhanced invasion capacity. Furthermore, the present study also revealed that nuclear translocation of PKM2, which is regulated by ERK pathway, regulated ß-catenin-TCF/LEF-1 transcriptional activity and associated EMT in HCC cell lines. These discoveries provide evidence of novel roles of PKM2 in the progression of HCC and potential therapeutic target for advanced cases.

The co-expression of ERß2 and IL-12Rß2 is better prognostic factor in non-small-cell lung cancer progression.

Estrogens and IL-12 play a pivotal role in the development and progression of non-small-cell lung cancer (NSCLC); at the same time, estrogen receptor ß2 and (interleukin-12 receptor ß2)IL-12Rß2 are their important receptors, respectively. With the functions of ERß2 and IL-12Rß2 explored further in NSCLC, some questions on the relation between ERß2 and IL-12Rß2 expression need to be solved. In this study, our aim is to elucidate relationship and roles of ERß2 and IL-12Rß2 in NSCLC. The expression of estrogen receptors ß2 and IL-12Rß2 was confirmed by Western blot and RT-PCR analysis in frozen tissues. The correlation between their expression levels and clinical characteristics was evaluated by Mann-Whitney and Kruskal-Wallis test. Using Kaplan-Meier plots and Cox proportional hazard models analyses, overall survival (OS) was evaluated. In contrast to benign pulmonary, ERß2 and IL-12Rß2 were over-expressed in NSCLC (p = 0.000). IHC results showed significant correlation between ERß2 and IL-12Rß2 (R = 0.382, p = 0.005). By analyzing the relation between ERß2, IL-12Rß2 mRNA expression levels and clinical characteristics, it was revealed that ERß2 and IL-12Rß2 were significant correlated with regional lymph node metastasis, T stage and clinical stage (p = 0.000/0.000; 0.001/0.000; 0.031/0.003 respectively), and both protein expression levels were lower with TNM stage being higher. In a Kaplan-Meier analysis, compared to both ERß2 and IL-12Rß2 or one low expression, high expression levels of ERß2 and IL-12Rß2 were identified in a group of patients with the longest overall survival (OS). Cox proportional hazard models revealed that ERß2 and IL-12Rß5 had longer OS. This is the first study to uncover that both ERß2 and IL-12Rß2 were over-expressed and further show that they were co-expressed in NSCLC. Moreover, we found that high expression levels of ERß2 and IL-12Rß2 may be positively correlated with OS and have prognostic values for the progression of NSCLC.

[Synthesis of 2-hydroxyl-5-butyramidobenzoic acid and its effect on acetic acid-induced colitis in rats].

OBJECTIVE: To study the method for synthesis of 2-hydroxyl-5- butyramidobenzoic acid and test its effect on acetic acid-induced colitis in rats. METHODS: 2-hydroxyl-5-butyramidobenzoic acid was synthesized from 5-aminosalicylic acid and butyric acid by amidation, esterification and hydrolization. The effect of 2-hydroxyl-5-butyramidobenzoic acid on acetic acid enema-induced colitis in rats was investigated. RESULTS: The structure of 2-hydroxyl-5-butyramidobenzoic acid was identified by IR and 1H-NMR. After treatment with acetic acid, the colon mucosal damage index (CMDI), fecal occult blood (OB) test, and activity of myelperoxidase (MPO) increased significantly in the rats as compared to the control levels. 2-hydroxyl-5- butyramidobenzoic acid obviously reduced the CMDI and OB, and reduced the level of MPO in the rats with colitis. CONCLUSION: The synthesis of 2-hydroxyl-5-butyramidobenzoic acid requires only mild conditions with simple procedures, and the synthesized 2-hydroxyl-5-butyramidobenzoic acid shows obvious therapeutic effects on mucosal damage of in rats with acetic acid-induced colitis.