IPA-3 inhibits the growth of liver cancer cells by suppressing PAK1 and NF-kB activation

Hepatocellular carcinoma (HCC) is one of the major malignancies worldwide and is associated with poor prognosis due to the high incidences of metastasis and tumor recurrence. Our previous study showed that overexpression of p21-activated protein kinase 1 (PAK1) is frequently observed in HCC and is associated with a more aggressive tumor behavior, suggesting that PAK1 is a potential therapeutic target in HCC. In the current study, an allosteric small molecule PAK1 inhibitor, IPA-3, was evaluated for the potential in suppressing hepatocarcinogenesis. Consistent with other reports, inhibition of PAK1 activity was observed in several human HCC cell lines treated with various dosages of IPA-3. Using cell proliferation, colony formation and BrdU incorporation assays, we demonstrated that IPA-3 treatment significantly inhibited the growth of HCC cells. The mechanisms through which IPA-3 treatment suppresses HCC cell growth are enhancement of apoptosis and blockage of activation of NF-κB. Furthermore, our data suggested that IPA-3 not only inhibits the HCC cell growth, but also suppresses the metastatic potential of HCC cells. Nude mouse xenograft assay demonstrated that IPA-3 treatment significantly reduced the tumor growth rate and decreased tumor volume, indicating that IPA-3 can suppress the in vivo tumor growth of HCC cells. Taken together, our demonstration of the potential preclinical efficacy of IPA-3 in HCC provides the rationale for cancer therapy.published_or_final_versio

Intuitionistic Fuzzy Time Series Functions Approach for Time Series Forecasting

Fuzzy inference systems have been commonly used for time series forecasting in the literature. Adaptive network fuzzy inference system, fuzzy time series approaches and fuzzy regression functions approaches are popular among fuzzy inference systems. In recent years, intuitionistic fuzzy sets have been preferred in the fuzzy modeling and new fuzzy inference systems have been proposed based on intuitionistic fuzzy sets. In this paper, a new intuitionistic fuzzy regression functions approach is proposed based on intuitionistic fuzzy sets for forecasting purpose. This new inference system is called an intuitionistic fuzzy time series functions approach. The contribution of the paper is proposing a new intuitionistic fuzzy inference system. To evaluate the performance of intuitionistic fuzzy time series functions, twenty-three real-world time series data sets are analyzed. The results obtained from the intuitionistic fuzzy time series functions approach are compared with some other methods according to a root mean square error and mean absolute percentage error criteria. The proposed method has superior forecasting performance among all methods

The tumor suppressive function of AMPK in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is one of the most common cancers in the world. However, the molecular mechanism underlying the development of HCC is still unclear. AMP-activated protein kinase (AMPK), which is a serine/theronine protein kinase, originally found as a key regulator in glucose and lipid metabolism in response to cellular stress. Recent publications suggest that AMPK activation results in suppressing cell proliferation. Also, AMPK lies upstream and downstream of two tumor suppressors, TSC2 and LKB1, respectively, indicating that AMPK may also involve in carcinogenesis. In this project, we aim to study the molecular mechanism leading to the tumor suppressive function of AMPK in HCC, particularly relating to the p53 pathway. Our preliminary findings have shown that overexpression of AMPKα2 catalytic subunit in HCC cell line HepG2 suppress cell proliferation in focus formation assay. On the other hand, an increase in proliferation rate was observed in HCC cell with AMPKα2 stably knocked down by small hairpin RNA. Also, our data have demonstrated that expression of constitutive active form of AMPKα2 leads to p53 phosphorylation at serine 15 residue and acetylation at lysine 382 residue. In addition, in-vitro kinase assay has shown that AMPK directly phosphorylates p53. Our results suggest that AMPK may mediate its tumor suppression function through regulation of p53

The tumor suppressive function of AMPK in Hepatocellular Carcinoma

Conference Theme: AMPK In Sickness And Health - From Molecule To Ma