دانلود رایگان مقاله لاتین مهار رشد تومور از سایت الزویر
عنوان فارسی مقاله:
پراواستاتین مهار رشد تومور از طریق بالا بردن سطح آپولیپوپروتئین A1
عنوان انگلیسی مقاله:
Pravastatin inhibits tumor growth through elevating the levels of apolipoprotein A1
سال انتشار : 2016
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مقدمه انگلیسی مقاله:
1. Introduction
Gastrointestinal tumors including gastric cancer (GC) and colorectal cancer (CRC) have been well recognized as tumors with high incidence and mortality worldwide [1,2]. Recently, targeted therapy using probing the overexpressed tumor markers has been demonstrated to have high effi- ciency in limiting tumor developments. The strategy also increased diagnostic accuracy in early stages of the above mentioned cancers [3,4]. In clinical practice, most patients with GC and CRC are diagnosed in advanced tumor stages with metastasis. Besides the limited diagnostic tools, it is urgent to develop and improve the therapeutic efficacy in tumor treatments. The poor prognosis of GC and CRC results from the lack of efficient therapeutic strategies. Statins are used for lowering plasma cholesterol levels as drugs treating coronary heart disease in clinical practice. The rationale of these agents is that they are competitive inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A (HMGCoA) reductase in the mevalonate pathway [5]. In addition to cholesterol lowering effects, statins have been well studied for their antitumor characteristics. For example, statins, except pravastatin, can inhibit breast tumor cell proliferation in vitro [6]. Moreover, a previous study has revealed that three kinds of statins including simvastatin, lovastatin, and pravastatin, can all inhibit esophageal adenocarcinoma cell proliferation through reducing farnesylation in protein targets such as Ras [7], indicating that statins have potential to aid chemotherapeutic agents in such tumor therapy. Because we noticed that the antitumor effects of statins are dependent on the types of tumors and importantly, on the performed statin dose [8,9], we are dedicated to discovering the antitumor mechanism of statins. In this study, we aimed to evaluate the tumor inhibitory effect of pravastatin, and to discover apolipoprotein A1 (ApoA1) as one of the putative tumor markers in gastrointestinal cancers. To our knowledge, statins can increase high-density lipoprotein (HDL) in serum [10] which possesses anti-inflammatory functions [11e13]. The most abundant component in HDL is ApoA1. A previous study has indicated that ApoA1 displays anti-inflammatory and antioxidant properties [14], revealing that ApoA1 may be an antitumor agent. Moreover, ApoA1 inhibits tumor cell proliferation in vitro, and reduces tumor growth in vivo in transgenic tumor models expressing ApoA1 [15,16]. It has been well documented that ApoA1 reduces the functions of activated neutrophils [17,18], and then diminishes the tumor cell proliferation due to neutrophils participation in tumor proliferation and metastasis [19]. Therefore, ApoA1 is expected to have antitumor effects through binding to lipidic growth factors and reducing inflammation derived from lymphocytes [15,16,18]. Our previous study indicated that ApoA1 levels were statistically decreased in the tumor regions of GC patients’ specimens using a proteomic two-dimensional difference gel electrophoresis technique [4]. We are therefore interested in dissecting the correlations of ApoA1 and tumorigenesis. To reboot the ApoA1 level, pravastatin was used and its antitumor effects were characterized and assessed. A previous study demonstrated that pravastatin slightly inhibits tumor cell proliferations [20], and significantly suppresses tumor growth in animal xenografts [9], concluding that pravastatin may have indirect effects on tumor proliferation. Moreover, another previous study demonstrated that ApoA1 decreases in larger tumors compared to that in smaller tumors in xenograft models, suggesting that ApoA1 is a downregulated marker of GC [21]. Moreover, the lower ApoA1 levels are associated with the tumor growth [20]. Therefore, increasing the ApoA1 levels in patients with GC may benefit the tumor therapy. We therefore administrated pravastatin to tumor xenografts to increase the ApoA1 levels, and to benefit the doxorubicin (DOX) chemotherapy, because statins have been demonstrated to synergize with DOX in ovarian cancer [22]. In order to improve the therapeutic efficiency of GC and CRC, this study specifically assumed biomarkers as a promising therapeutic strategy. Therefore, ApoA1 was investigated in this study as the biomarker of GC and CRC. We performed ApoA1 to inhibit tumor cell proliferation, and also elucidated that ApoA1 functioned to reduce tumor growth. Furthermore, the treatment combined with pravastatin and DOX largely reduced tumor volume in tumor xenografts. The pravastatin-mediated antitumor effects may be associated with the increased amount of ApoA1. In conclusion, the targeted therapy for suppressing inflammation through increasing ApoA1 by pravastatin may be promising for tumor treatment.
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کلمات کلیدی:
Braunwald's Heart Disease E-Book: A Textbook of Cardiovascular Medicine https://books.google.com/books?isbn=1437727700 Robert O. Bonow, Douglas L. Mann, Douglas P. Zipes - 2011 - Medical Other mutations of apo A-I lead to an increased catabolic rate of apo A-I and may not be ... Patients without CETP have very elevated HDL cholesterol levels, enriched in ... Using mendelian randomization principles, mutations of the ABCA1 gene ... Growth hormone can reduce LDL cholesterol and augment HDL cholesterol ... The Cardioprotective Protein Apolipoprotein A1 Promotes Potent Anti ... www.jbc.org/content/288/29/21237.full by M Zamanian-Daryoush - 2013 - Cited by 60 - Related articles Jul 19, 2013 - Results: ApoA1 suppresses tumor growth and metastasis, primarily via .... Plasma (EDTA) or serum levels of human apoA1 were determined using an .... increasing apoA1 levels, with A1KO mice showing the greatest rates of ... Clinical Approach to Sudden Cardiac Death Syndromes https://books.google.com/books?isbn=1848829272 Ramon Brugada - 2010 - Medical The clinical usefulness of apolipoprotein levels has stirred debate. Although a useful research tool in general, the measurement of apolipoproteins AI and B ... with elevated plasma triglycerides and reduced HDL cholesterol levels.21 It ... Growth hormone can reduce LDL cholesterol and augment HDL cholesterol but is not ... Treatment of the Postmenopausal Woman: Basic and Clinical Aspects https://books.google.com/books?isbn=0080553095 Rogerio A. Lobo - 2007 - Medical levels below baseline values. ... a negative effect on breast cancer growth is mediated via the androgen receptor (113). ... adversely affect serum levels of HDL-cholesterol and apolipoprotein A1. ... Androgens may elevate serum levels of oxyphenbutazone and may rarely affect insulin requirements in diabetic patients. Dietary Fat and Cancer: Genetic and Molecular Interactions https://books.google.com/books?isbn=1475726708 American Institute for Cancer Research - 2013 - Science trans-activation studies using the apo A-I gene upstream elements suggest that ... a level of 0.1% or less and the weaker chemicals di(2-ethylhexyl)phthalate and ... markedly increase fatty acid 3-oxidation but only modestly elevate catalase, ... Recent Advances in Digestive Medicine Articles - Elsevier https://www.journals.elsevier.com/advances-in-digestive-medicine/recent-articles Higher net change of index of hemoglobin values between colon polyp and nonpolyp ..... inhibits tumor growth through elevating the levels of apolipoprotein A1. Searches related to growth through elevating the levels of apolipoprotein A1 apolipoprotein a1 low apolipoprotein a1 deficiency apolipoprotein b hscrp
