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Zhang W.,Institute of Endocrinology and Diabetology | Zhang W.,Fudan University | Hu R.,Institute of Endocrinology and Diabetology | Hu R.,Fudan University
Medical Hypotheses | Year: 2010

Prostate cancer (CaP) is one of the most common types of cancer among men and the second leading cause of cancer-related death in western countries. The risk factors for CaP are age, race/ethnicity, family history and diet. It is interesting that epidemiologic evidence suggests a history of diabetes mellitus (DM) is related to a decreased CaP risk. The cause of this association remains largely unknown. DM is a group of metabolic diseases characterized by hyperglycemia and insulin resistance. It is commonly associated with microvascular complications including diabetic retinopathy, nephropathy and neuropathy. The typical histological changes of microvascular lesions are capillary basement membrane thickening, capillary occlusion and degeneration, eventually capillary dysfunction and organ ischemia. Therefore, we hypothesize that DM might induce local microvascular dysfunction and prostate ischemia, which prevent initiation and development of CaP. Currently, numerous studies showing effect of anti-angiogenesis therapy on CaP strongly support our hypothesis. © 2009 Elsevier Ltd. All rights reserved.

Feng X.,Institute of Endocrinology and Diabetology | Feng X.,Fudan University | Lu B.,Institute of Endocrinology and Diabetology | Xu Y.,Fudan University | And 6 more authors.
International Journal of Molecular Medicine | Year: 2011

Previous studies on the apoptotic effect of aspirin mainly focus on colorectal cancer and breast carcinoma. Few studies have been designed to explore the effect of aspirin on hepatocellular carcinoma. In the present study, we observed that aspirin caused G0/G1 phase cell cycle arrest and reduced etoposide induced caspase-3 activation in hepatocellular carcinoma G2 (HepG2) cells. Further investigation demonstrated that aspirin notably enhanced the activity of Akt and ERK1/2. Blocking the activation of Akt by the PI3-K-selective inhibitor wortmannin abrogated the anti-apoptotic effect of aspirin while the MEK inhibitor U0126 did not. p21 cip, an important substrate of Akt, is involved in the regulation of cell cycle arrest and apoptosis. Our data showed that the protein expression and ser146 phosphorylation levels of p21 cip were significantly increased after treatment with aspirin, whereas p53 or p27 showed no change. The increase of p21 cip protein levels was also scavenged by wortmannin but not by U0126. Moreover, reduction of caspase-3 activity induced by aspirin was attenuated by silencing p21 cip expression. These results indicated that the anti-apoptotic effect of aspirin was dependent on activation of Akt which inhibited cell apoptosis by up-regulating p21 cip and blocking caspase-3 activation. These findings could have clinical relevance in anticancer therapy and aspirin co-treatment of human malignancies.

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