Lung Adenocarcinoma Tumor Growth Research Articles

Expression Profiling Identifies Bezafibrate as Potential Therapeutic Drug for Lung Adenocarcinoma.

Drug-induced gene expression patterns that invert disease profiles have recently been illustrated to be a new strategy for drug-repositioning. In the present study, we validated this approach and focused on prediction of novel drugs for lung adenocarcinoma (AC), for which there is a pressing need to find novel therapeutic compounds. Firstly, connectivity map (CMap) analysis computationally predicted bezafibrate as a putative compound against lung AC. Then this hypothesis was verified by in vitro assays of anti-proliferation and cell cycle arrest. In silico docking evidence indicated that bezafibrate could target cyclin dependent kinase 2(CDK2), which regulates progression through the cell cycle. Furthermore, we found that bezafibrate can significantly down-regulate the expression of CDK2 mRNA and p-CDK2. Using a nude mice xenograft model, we also found that bezafibrate could inhibit tumor growth of lung AC in vivo. In conclusion, this study proposed bezafibrate as a potential therapeutic option for lung AC patients, illustrating the potential of in silico drug screening.

190P - Microrna-29A Suppresses Growth, Migration and Invasion of Lung Adenocarcinoma By Targeting Carcinoembryonic Antigen-Related Cell Adhesion Molecule 6

ABSTRACT Aim: Carcinoembryonic antigen-related cell adhesion molecule (CEACAM)6 is the important regulator in cell adhesion, invasion and metastasis. MicroRNAs (miRNAs), a group of small non-coding RNAs that regulate the expression of many genes can act as oncogenes and tumor suppressors. The aim of this study was to evaluate the functional roles of CEACAM6 in lung adenocarcinoma and to identify miRNAs that could inhibits the growth, migration and invasion of lung adenocarcinoma by targeting CEACAM6. Methods: The expression of CEACAM6 in lung adenocarcinoma tissues was detected by immunohistochemistry. Cell proliferation, migration and invasion assays in A549 cell lines were performed in vitro and the A549 xenograft models were used for in vivo analysis. Bioinformatics prediction, western blot and luciferase assay were identified the target of miRNA. Results: Patients with low expression of CEACAM6 protein had significant longer overall survival, compared with those with high expression of CEACAM6 protein. The knockdown of CEACAM6 suppressed cell proliferation, migration and invasion, whereas CEACAM6 overexpression increased proliferation, migration and invasion in vitro. These findings are consistent with results of in vivo xenograft experiments. The relative luciferase activity was significantly decreased by miR-29a that was potentially targeting CEACAM6 using miRNA target predicting program in A549 cells co-transfected with wild type CEACAM6-3'-UTR, whereas the luciferase activity was not suppressed by the vector containing the mutant 3'-UTR or negative vector. Furthermore, miR-29a suppressed cell proliferation, migration and invasion in vitro and inhibited tumor growth of lung adenocarcinoma in vivo. Conclusions: miR-29a can suppress tumor growth, migration and invasion of lung adenocarcinoma by targeting CEACAM6, which may provide a potential therapeutic target for treatment of lung adenocarcinoma. Disclosure: All authors have declared no conflicts of interest.

Reduced expression of Krüppel-like factor 17 is related to tumor growth and poor prognosis in lung adenocarcinoma

Krüppel-like factor 17 (KLF17), a new member of the Krüppel-like factors (KLFs), has been reported to be a negative regulator of epithelial-mesenchymal transition (EMT) and metastasis in breast cancer. However, the biological role and clinical significance of KLF17 in lung adenocarcinoma has been less clear. In the present study, we showed that KLF17 expression was decreased in lung adenocarcinoma. Reduced expression of KLF17 was correlated significantly with a short survival time in patients with lung adenocarcinoma (P<0.0001). Moreover, KLF17 expression was an independent prognostic indicator for patients with lung adenocarcinoma. KLF17 expression level was correlated with the tumor stage (P=0.016) and tumor size (P=0.001) in lung adenocarcinoma. Overexpression of KLF17 inhibited cell growth in A549 and PC-9 cell lines. In conclusion, it is possible that KLF17 inhibits tumor growth in lung adenocarcinoma. The reduced expression of KLF17 is a valuable prognostic indicator for patients with lung adenocarcinoma, and KLF17 could be a novel target for treatment of lung adenocarcinoma.

ERα expression phenotype determines the effects of estrogen and benzo[a]pyrene on lung adenocarcinoma tumor growth

ERα expression phenotype determines the effects of estrogen and benzo[a]pyrene on lung adenocarcinoma tumor growth

Ing4 induces Cell Growth Inhibition in Human Lung Adenocarcinoma A549 Cells by Means of Wnt‐1/β‐Catenin Signaling Pathway

ING4, as a novel candidate tumor suppressor gene, has been implicated in several human malignances by tumor growth inhibition and apoptosis enhancement. The mechanism of ING4 remains largely unknown. The purpose of this study was to investigate the inhibitory tumor growth effects of ING4 on lung adenocarcinoma, and its mechanism, by ING4 cDNA transduction into A549 cells. Furthermore, the expression level of ING4 in lung adenocarcinoma tissues was examined. The expression of ING4 was markedly reduced in human lung adenocarcinoma tissues. Overexpression of ING4 can induce growth inhibition in A549 cells both in vitro and in vivo, and also induce up-regulation of p27, down-regulation of cyclinD1, SKP2, and Cox2, and inactivation of the Wnt-1/beta-catenin pathway. Moreover, overexpression of ING4 can enhance the sensitivity of A549 cells to radiotherapy and chemotherapy. Thus, ING4 may play an inhibitory role on A549 cell proliferation and tumor growth in lung adenocarcinoma by up-regulation or down-regulation of cell proliferation-regulating proteins such as p27, cyclinD1, SKP2, and Cox2 by means of inactivation of Wnt-1/beta-catenin signaling.

Alpha-Chemokine growth factors for adenocarcinomas; a synthetic peptide inhibitor for alpha-chemokines inhibits the growth of adenocarcinoma cell lines.

The experiments aimed to determine if alpha-chemokine inhibitors are effective suppressors of the growth of adenocarcinomas, a neoplasm with a high mortality rate. Expression of growth-related oncogene (GROalpha) and interleukin-8 (IL-8) was determined by enzyme-linked immunosorbent assay. Inhibition of alpha-chemokine binding to tumor cells was assessed in the presence and absence of the hexapeptide, antileukinate. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays were performed to determine the effect of alpha-chemokines, monoclonal antibodies (mAb), and antileukinate on cell proliferation. Finally, antileukinate inhibition of human, lung adenocarcinoma tumor growth, was determined in BALB/c nude mice. All of the adenocarcinomas tested produced either GROalpha or IL-8 or both. Proliferation of lung, stomach and colon adenocarcinoma cells was inhibited by anti-GROalpha mAb and/or anti-IL-8 mAb while recombinant human GROalpha stimulated the proliferation of lung and stomach adenocarcinomas. Antileukinate inhibited GROalpha binding to specific receptors on adenocarcinoma cells and inhibited the proliferation of all adenocarcinomas tested. Colon-derived adenocarcinomas specifically bound IL-8 and this binding was also inhibited by antileukinate. Administration of antileukinate in vivo inhibited the tumor growth of adenocarcinoma A549. GROalpha and IL-8 are necessary for the growth of lung, stomach and colon adenocarcinomas, and can be inhibited by the hexapeptide, antileukinate. The findings suggest the possibility of using alpha-chemokine receptor inhibitors in the treatment of adenocarcinoma.