Open AccessPravastatin inhibits tumor growth through elevating the levels of apolipoprotein A1
Author(s) -
Yeh Chun,
Cheng ChunChia,
Lin HuaChing,
Luo TsaiYueh,
Chang Jungshan,
Ho AiSheng
Publication year - 2016
Publication title -
advances in digestive medicine
Language(s) - English
Resource type - Journals
ISSN - 2351-9800
DOI - 10.1016/j.aidm.2015.03.003
Subject(s) - pravastatin , medicine , hmg coa reductase , cancer research , cancer , pharmacology , in vivo , colorectal cancer , cholesterol , endocrinology , chemistry , biology , enzyme , reductase , biochemistry , microbiology and biotechnology
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.