دانلود رایگان مقاله پراواستاتین مهار رشد تومور با بالا بردن سطح آپولیپوپروتئین A1

Summary

Background: Statins are a class of drugs used to lower cholesterol levels, accompanying increased high-density lipoprotein (HDL) levels. Previous studies have suggested that statins can inhibit inflammation, and also reduce tumor proliferation. We therefore hypothesized that pravastatin, a member of the statins, mediating the inhibitory functions in tumor growth may be associated with the upregulated HDL constituent, apolipoprotein A1 (ApoA1). Methods: Pravastatin-induced inhibition in tumor proliferation in vitro and in xenografts was investigated. Reduced ApoA1 expressions were detected in the tumor regions in specimens from tumor patients as well in xenografts using Western Blotting. Moreover, ApoA1 was administered to inhibit tumor proliferation, and pravastatin was given to enhance the chemotherapeutic efficacy of doxorubicin (DOX). Results: We found a significant statistical reduction of ApoA1 in the tumor regions of specimens from gastric cancer and colorectal cancer patients. MKN45 cells proliferation was inhibited by 18% under the growing medium containing pravastatin. ApoA1 levels were elevated in liver Clone 9 cells administered pravastatin, but not in MKN45 cells. In vitro studies revealed that ApoA1 can reduce MKN45 tumor proliferation. Moreover, the tumor volume was significantly reduced in in vivo xenografts after the administration of pravastatin. Combined treatments of pravastatin with DOX significantly minimized the size of tumors, leading to a better therapeutic efficacy. Conclusion: This study demonstrated that pravastatin elevated ApoA1, an HDL major constituent with anti-inflammatory characteristics, which displayed strong adversary associations with tumor developments and growth. Increasing the amounts of ApoA1 by pravastatin coupled with DOX may improve the therapeutic efficacy for cancer treatment.

Discussion

This study aimed to evaluate the inhibitory effect of pravastatin on tumor growth and progression, and tried to uncover the molecular mechanism of pravastatin in tumor therapy. Because pravastatin is a HDL inducer [26,27], in HDL the major component is ApoA1, we therefore measured the pravastatin-induced ApoA1 expression and evaluated the pravastatin-induced antitumor effect. ApoA1 has been reported to have the capacity to inhibit tumor growth through binding to lipidic growth factors [15] and suppressing neutrophil activity [17,18,28] which may modulate tumor development. In this study, we demonstrated that pravastatin not only elevated ApoA1 levels and inhibited tumor growth, but also benefited the DOX inhibitory effect in vivo.