Abstract. emodin (1, 3, 8-trihydroxy-6-methylanthraquinone) is an active constituent isolated from the root of Rheum palmatum l and is the main effective component of some chinese herbs and plants. pharmacological studies have demonstrated that emodin exhibits anti-cancer effects on several human cancers. However, the molecular mechanisms of emodin-mediated tumor regression have not been fully defined. This study was performed to investigate the antiproliferative and antimetastatic effects of emodin on pancreatic cancer in vitro and in vivo. our results showed that emodin induced a higher percentage of growth inhibition and apoptosis in the pancreatic cancer cell line sW1990 compared to that of control, and emodin suppressed the migration and invasion of sW1990 cells in a dose-dependent manner. to investigate the possible mechanisms involved in these events, we performed electrophoretic mobility shift assay (eMsA) and Western blot analysis, and found that emodin significantly down-regulated NF-κB DnA-binding activity, survivin and MMp-9 in sW1990 cells. Moreover, the expression of cleaved caspase-3 was up-regulated in sW1990 cells after treatment with emodin. In addition, a metastatic model simulating human pancreatic cancer was established by orthotopic implantation of histologically intact human tumor tissue into the pancreatic wall of nude mice. oral administration of emodin significantly decreased tumor weight and metastasis compared to control. Furthermore, the expression of NF-κB, survivin and MMp-9 were also suppressed in tumor tissues after treatment with emodin. collectively, our results indicated that emodin exerts antiproliferative and antimetastatic activity on pancreatic cancer both in vitro and in vivo, which may be related to down-regulation of NF-κB and its regulated molecules such as survivin and MMp-9 proteins. consequently, these results provide important insights into emodin as an anti-invasive agent for the therapy of human pancreatic cancer.

Emerging studies have indicated that leucine-rich repeat kinase 2 (LRRK2) is associated with thyroid cancer (TC). The present study investigated the effect of LRRK2 on the cell cycle and apoptosis in TC, and examined the underlying mechanisms in vitro . To screen TC-associated differentially expressed genes, gene expression microarray analysis was conducted. Retrieval of pathways associated with TC from the Kyoto Encyclopedia of Genes and Genomes database indicated that the c-Jun N-terminal kinase (JNK) signaling pathway serves an essential role in TC. SW579, IHH-4, TFC-133, TPC-1 and Nthy-ori3-1 cell lines were used to screen cell lines with the highest and lowest LRRK2 expression for subsequent experiments. The two selected cell lines were transfected with pcDNA-LRRK2, or small interfering RNA against LRRK2 or SP600125 (a JNK inhibitor). Subsequently, flow cytometry, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling, a 5-ethynyl-2′-deoxyuridine assay and a scratch test was conducted to detect the cell cycle distribution, apoptosis, proliferation and migration, respectively, in each group. The LRRK2 gene was determined to be elevated in TC based on the microarray data of the GSE3678 dataset. The SW579 cell line was identified to exhibit the highest LRRK2 expression, while IHH-4 cells exhibited the lowest LRRK2 expression. LRRK2 silencing, through inhibiting the activation of the JNK signaling pathway, increased the expression levels of genes and proteins associated with cell cycle arrest and apoptosis in TC cells, promoted cell cycle arrest and apoptosis, and inhibited cell migration and proliferation in TC cells, indicating that LRRK2 repression could exert beneficial effects through the JNK signaling pathway on TC cells. These observations demonstrate that LRRK2 silencing promotes TC cell growth inhibition, and facilitates apoptosis and cell cycle arrest. The JNK signaling pathway may serve a crucial role in mediating the anti-carcinogenic activities of downregulated LRRK2 in TC.

No abstract