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Xu Y.,Jiangsu University | Jin J.,Jiangsu University | Zhang W.,Jiangsu University | Zhang Z.,Jiangsu University | And 7 more authors.
Carcinogenesis | Year: 2015

Dysregulated expression of epidermal growth factor receptor (EGFR) has been implicated in many cancer events, while peroxisome proliferator-activated receptor γ (PPARγ) negatively regulates cancer progression. The molecular mechanism of EGFR interaction with PPARγ is still unclear. Here, we found that nuclear EGFR induced phosphorylation of PPARγ at Tyr-74 leading to PPARγ ubiquitination and degradation by mouse double minute 2 (MDM2) ubiquitin ligase. PPARγ degradation by EGFR/MDM2 signaling resulted in accumulation of nuclear factor-kappaB (NF-κB)/p65 protein levels and increasing NF-κB activation. In contrast, PPARγ-Y74A mutant reversed this event. Moreover, PPARγ-Y74A mutant suppressed cell proliferation and increased chemotherapeutic agent-induced cancer cell sensitivity. Importantly, the clinical findings show that the nuclear phosphorylation of PPARγ-Y74 and EGFR expression in colonic cancer tissues was higher than that in control normal tissues. Thus, our study revealed a novel molecular mechanism that nuclear EGFR/NF-κB signaling promoted cell proliferation by destructing PPARγ function, which provides a novel strategy for cancer treatment. © Crown copyright 2015.


Wang Y.,Jiangsu Taizhou Peoples Hospital | Ye H.,Affiliated Hospital of Guiyang Medical College | Yin H.,Central University of Costa Rica
Current Signal Transduction Therapy | Year: 2015

Tetrandrine (Ted) has been demonstrated in a series of studies to have potential antitumor effect against several cancers. Its lipophilicity makes it an ideal model drug for nanoparticle encapsulation. We constructed Ted loaded nanoparticles (Ted-NP) with PLGA-PEG as drug carrier. Characterization of the nanoparticles showed that Ted-NP had a size of less than 100 nm and a slight negative surface charge. By adjusting the feeding ratio, the highest drug loading content and encapsulation efficiency were 13.6% and 87.2%, respectively. In vitro release indicated the sustained release pattern of Ted-NP. In vitro cytotoxicity test demonstrated that Ted-NP showed stronger cell growth inhibitory effect than free Ted did at equivalent doses. The antitumor effect was mediated by induction of apoptosis through a mitochondrial way. Therefore, the characteristic of amphiphilic copolymer based drug delivery system enables a more efficient way to deliver Ted for cancer treatment. © 2015 Bentham Science Publishers.


Lu K.-J.,Jiangsu Taizhou Peoples Hospital | Wu X.-L.,Nanjing Medical University | Chen C.,Nanjing University of Traditional Chinese Medicine | Huang X.-E.,Jiangsu Cancer Hospital and Research Institute | Yin H.-T.,Central University of Costa Rica
Asian Pacific Journal of Cancer Prevention | Year: 2014

Purpose: Lung cancer, one of the most frequently diagnosed cancers in the world, is characterized by relatively high morbidity and mortality. Berbamine (BER) has been initially reported to exert anti-proliferative effects against a series of cancers. Methods: In this study the in vitro cytotoxicity of BER was measured by MTT assay. In vivo anti-cancer efficacy of BER was assessed in A549 xenografts. Results: Cytotoxicity tests showed dose-dependent cell growth inhibition effects of BER against A549 cells. Moreover, BER significantly reduced the growth of lung cancer in a dose-dependent manner in nude mice with prolonged survival time. Conclusion: Therefore, BER might be in herbal medicine for cancer therapy and further efforts are needed to explore therapeutic strategies.


Chen X.,Fudan University | Chen X.,China Medical City Institute of Health science | Li S.,Fudan University | Li S.,China Medical City Institute of Health science | And 10 more authors.
Journal of Thrombosis and Haemostasis | Year: 2012

Background: Genetic variants influencing lipid levels and risk of coronary artery disease (CAD) have been identified by recent genome-wide association studies (GWAS). Objectives: To test the association of single nucleotide polymorphisms (SNPs) implicated in lipoprotein metabolism and CAD in GWAS with atherosclerotic cardiovascular disease (ASCVD, including ischemic stroke [IS] and myocardial infarction [MI] phenotypes). Patients and methods: A two-stage genetic association study was conducted in the Chinese Hans population. Stage I included a cohort with 451 IS cases and 462 controls for association analysis using 92 SNPs. Stage II examined the associations of eight positive variants and five additional variants with IS, MI and ASCVD in a cohort with 779 IS cases and 836 controls and a cohort with 824 MI cases and 737 controls. Results: The T allele of rs4731702 located near the KLF14 gene was associated with a decreased risk of MI with an odds ratio (OR) of 0.72 (P<3.85×10-3). The rs4731702-T allele was also associated with a decreased risk of ASCVD with an OR of 0.78 (Pmeta-analysis<5.43×10-4). In addition, we found that a missense variant of KLF14, rs111400400 (Ser58Pro), was associated with MI. Conclusion: Genetic variants newly identified near/in the KLF14 gene were implicated in the aetiology of atherosclerotic-related phenotypes. © 2012 International Society on Thrombosis and Haemostasis.


Yi S.-H.,Xinyu Peoples Hospital | Zhang Y.,Jiangsu Taizhou Peoples Hospital | Tang D.,Changzheng Hospital | Zhu L.,Changzheng Hospital
Biotechnology Letters | Year: 2015

Objectives: Hepatic stellate cells (HSCs), the principal producers of extracellular matrix proteins, play a major role in the development of liver fibrosis which is accompanied with elevated sinusoidal pressure and portal hypertension. We have isolated primary rat HSCs and investigated the effect of mechanical pressure and tensile strain on retinol metabolism in the cells. Results: Mechanical force and tensile strain significantly increased the expression of α-smooth muscle actin (α-SMA) and collagen I, and notably inhibited the expression of cellular retinol-binding protein I (CRBP-I), lecithin-retinol acyltransferase (LRAT), retinyl ester hydrolase (REH), retinoic acid receptor-β (RAR-β) and retinoid X receptor-α (RXR-α). Such effects were partially reversed by the retinoid X receptor antagonist, HX531, and the retinoic acid receptor antagonist, LE135. Conclusion: Mechanical force and tensile strain significantly activate HSCs by regulating the retinoid metabolic pathway. Activation of HSCs can therefore be manipulated through mechanical force and tensile strain in vitro. © 2015, Springer Science+Business Media Dordrecht.

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