Dataset Information

SU11274 suppresses proliferation and motility of pancreatic cancer cells.

ABSTRACT: Mesenchymal-epithelial transition factor (c-Met) is associated with the proliferation and motility of cancer cells. c-Met expression has been detected in surgical pancreatic cancer specimens, and its overexpression is associated with a poor prognosis. SU11274 is a specific inhibitor of c-Met. In the present study, the cell proliferation and motility of pancreatic cancer cells treated with SU11274 was investigated. The PANC-1, MIA-Paca2, NOR-P1, PK-45H, PK-1 and PK-59 pancreatic cancer cell lines were used. The expression of c-Met and cyclin D1 was analyzed by quantitative polymerase chain reaction. In addition, a 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium inner salt assay was performed to assess cell proliferation, and a scratch assay was performed to assess cell motility. c-Met expression was higher in PANC-1, PK-45H, PK-1 and PK-59 cell lines compared with that in normal pancreatic tissue. Following treatment with 30 µM SU11274, the proliferation of MIA-Paca2 and PK-45H cells was suppressed to 19.8±10.7% (P<0.05) and 45.8±14.8% (P<0.05) of the control level, respectively. Furthermore, cyclin D1 expression was downregulated to 43.7±17.9% (P<0.05) and 53.2±18.6% (P<0.05) of the control level in the MIA-Paca2 and PK-45H cell lines, respectively, following treatment with 30 µM SU11274. In addition, cell motility was reduced to 1.0±0.3% in MIA-Paca2 (P<0.05) and 14.7±3.5% in PK-45H (P<0.05) following treatment with 30 µM SU11274, compared with the motility of untreated cells. These results indicated that SU11274 suppresses the proliferation of pancreatic cancer cells via the downregulation of cyclin D1. The present study also demonstrated that cell motility was suppressed by treatment with SU11274.

SUBMITTER: Tomizawa M

PROVIDER: S-EPMC4533741 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

SU11274 suppresses proliferation and motility of pancreatic cancer cells.

Tomizawa Minoru M Shinozaki Fuminobu F Motoyoshi Yasufumi Y Sugiyama Takao T Yamamoto Shigenori S Ishige Naoki N

Oncology letters 20150702 3

Mesenchymal-epithelial transition factor (c-Met) is associated with the proliferation and motility of cancer cells. c-Met expression has been detected in surgical pancreatic cancer specimens, and its overexpression is associated with a poor prognosis. SU11274 is a specific inhibitor of c-Met. In the present study, the cell proliferation and motility of pancreatic cancer cells treated with SU11274 was investigated. The PANC-1, MIA-Paca2, NOR-P1, PK-45H, PK-1 and PK-59 pancreatic cancer cell lines ...[more]

PMID: 26622692

Similar Datasets

Project description:Background: Targeting inflammatory microenvironment is a promising anti-tumor strategy. Paeonol is a phenolic compound with effective anti-inflammatory and anti-tumor properties. However, the effects of paeonol on non-small cell carcinoma (NSCLC) have not been fully investigated. Here, we evaluated the effects of paeonol on proliferation and metastasis of NSCLC and elucidated the underlying mechanisms. Methods: The effects of paeonol on inflammatory cytokines were determined by cell proliferation and ELISA assays. Assays of wound healing, single cell migration and perforation invasion were used to evaluate migration and invasion of NSCLC cells. Expression of marker proteins in epithelial-mesenchymal transition (EMT) and matrix metalloproteinase (MMP) family enzymes were detected by Western blot assays. Nude mouse A549 cells transplantation tumor model was used to study the anti-lung cancer effects of paeonol in vivo. TUNEL stanining were used to detect the apoptosis of tumor cells in A549 lung cancer mice, and Ki67 analysis was used to detect the proliferation of tumor cells in A549 lung cancer mice. Immunohistochemistry was used to detect the effects of paeonol on signaling molecules in tumor tissues. Results: Paeonol inhibited A549 cancer cell migration and invasion in vitro. Paeonol inhibited secreaion of inflammatory cytokines in A549 cells, including tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1β, and transforming growth factor (TGF)-β. Paeonol altered the expression of marker proteins involved in EMT and MMP family enzymes. In addition, paeonol inhibited the transcriptional activity of nuclear factor-κB (NF-κB) and phosphorylation of signal transducers and activators of transcription 3 (STAT3). Paeonol inhibited the growth of A549 cells transplanted tumors in nude mice. Conclusion: Paeonol potently inhibited NSCLC cell growth, migration and invasion associated with disruption of STAT3 and NF-κB pathways, suggesting that it could be a promising anti-metastatic candidate for tumor chemotherapy.

Project description:BackgroundPancreatic cancer (PC) is one of the most lethal solid malignancies in the world due to its excessive cell proliferation and aggressive metastatic features. Emerging evidences revealed the importance of posttranscriptional modifications of RNAs in PC progression. However, knowledge about the 5-methylcytosine (m5C) RNA modification in PC is still extremely limited. In this study, we attempted to explore the expression changes and clinical significances of 12 known m5C-related genes among PC patients.MethodsA total of 362 normal and 382 tumor specimens from PC patients were examined for candidate m5C-related gene and protein expression by using quantitative PCR (qPCR) and immunohistochemistry (IHC). The proliferation rate of PC cells was detected by MTS assay. Xenograft mouse models were used to assess the role of NSUN6 in PC tumor formation.FindingsThrough analyzing the four Gene Expression Omnibus (GEO) databases, six m5C-related genes shown significant and consistent alterations were selected for further examination in our 3 independent PC cohorts. Finally, we identified the reduction of NSUN6 as a common feature of all PC sample sets examined. NSUN6 expression correlated with clinicopathologic parameters including T stage, and Ki67+ cell rate. Further assessing the transcriptional profiles of 50 PC tissues, we found biological processes associated with cell proliferation like cell cycle and G2M checkpoint were enriched in NSUN6 lower expression group. Helped by in vitro PC cell lines and in vivo xenograft mouse models, we confirmed the role of NSUN6 in regulating cell proliferation and PC tumor growth. Last but also importantly, we also show the good performance of NSUN6 in evaluating tumor recurrence and survival among PC patients.InterpretationOur data suggested that NSUN6 is an important factor involved in regulating cell proliferation of PC, and highlights the potential of novel m5C-based clinical modalities as a therapeutic approach in PC patients.FundingThis study was supported by the National Natural Science Foundation of China (Grant Nos. 81803014, 81802424, and 81802911).

Dataset Information

SU11274 suppresses proliferation and motility of pancreatic cancer cells.

Publications

SU11274 suppresses proliferation and motility of pancreatic cancer cells.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets