N-myc downstream-regulated gene 1 (NDRG1) is known as tumor/metastasis suppressor in a variety of cancers including pancreas, being involved in angiogenesis, cancer growth and metastasis. However, the precise molecular mechanism how NDRG1 exerts its inhibitory function in pancreatic cancer remains unclear. In this investigation, we demonstrated that K-Ras plays a vital role in modulating NDRG1 protein level in PDAC cancer cells in vitro, which is mediated through ERK signaling. Noteworthy, K-Ras downstream Akt/mTOR signaling is inhibited upon NDRG1 overexpression, resulting in decease of HIF1α level. Moreover, NDRG1 has a unique role in modulating cancer metabolism of pancreatic ductal adenocarcinoma (PDAC). The mechanism accounting for NDRG1 in modulating aerobic glycolysis, at least partly, relied on its regulation of glycolysis genes including GLUT1, HK2, LDHA and PDK1. Additionally, NDRG1 is shown to suppress the activity of HIF1α, which is responsible for regulation of glycolysis enzymes. The current study is the first to elucidate a unique facet of the potent tumor/metastasis suppressor NDRG1 in the regulation of PDAC glycolysis, leading to important insights into the mechanism by which NDRG1 exert inhibitory function in PDAC.

Emodin is an anthraquinone isolated from the Chinese herb Radix et Rhizoma Rhei and has been used to treat various diseases for centuries. The aim of the present study was to investigate the effect of emodin on the inflammatory mediators in rat chondrocytes. In the present study, chondrocytes were isolated from rats, cultured and harvested when they reached generation P3. Cells were treated with different doses of emodin (10, 20, and 30 µg/ml) followed by interleukin 1β (IL‑1β, 10 ng/ml). Control cells were either untreated or treated with IL‑1β alone. An enzyme‑linked immunosorbent assay was used to measure levels of nitric oxide (NO) and prostaglandin E2 (PGE2). Reverse transcription‑quantitative polymerase chain was performed to measure levels of matrix metallopeptidase (MMP)‑3 and ‑13 mRNA. The expression of MMP‑3, MMP‑13, extracellular‑signal regulatory kinase (ERK)1/2, phosphorylated ERK1/2 and β‑catenin proteins were detected by western‑blot analysis. The results demonstrated that treatment with emodin treatment reduced the cytotoxicity of IL‑1β and inhibited the expression of NO and PGE2 in rat chondrocytes. Furthermore, emodin inhibited the expression of MMP3 and MMP13, and the phosphorylation of various proteins involved in the ERK and Wnt/β‑catenin pathway. Therefore, emodin is able to promote the proliferation of chondrocytes by inhibiting the ERK and Wnt/β‑catenin pathway and downregulating the expression of a series of inflammatory mediators in chondrocytes.

To determine the expressions of Tbx3, a member of subgroup belonging to T-box family, and its prognostic value in pancreatic carcinoma. We determined the expression levels of Tbx3 on both mRNA and protein levels in 30 pairs of fresh tumor tissues and paratumor tissues by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting, respectively. In addition, protein level of Tbx3 were identified using immunochemistry in 80 pairs of paraffin-embedded specimen. The correlations between Tbx3 expression and various clinicopathological parameters as well as overall survival were evaluated. Tbx3 mRNA and protein levels in tumor tissues were significantly higher than in the paratumor tissues by qRT-PCR (0.05 ±0.007 vs. 0.087±0.001, p<0.001) and western blotting (1.134±0.043 vs. 0.287±0.017, p<0.001). The statistical analysis based on immunohistochemical evaluation suggested that Tbx3 aberrant expression was significantly associated with several conventional clinicopathological variables, such as gender, age, tumor position, preoperative CA19-9 level, pathological T staging and N staging. Univariate and multivariate analyses revealed that Tbx3 expression was an independent prognostic factor for overall survival (<0.001). Our results suggest that overexpression of Tbx3 is associated with poor prognosis of pancreatic cancer patients. However, additional clinical trials are needed to accurately validate this observation.