Pravastatin inhibits tumor growth through elevating the levels of apolipoprotein A1

ADVANCES IN DIGESTIVE MEDICINE - Tập 3 - Trang 3-10 - 2016
Chun Yeh1, Chun-Chia Cheng2, Hua-Ching Lin3, Tsai-Yueh Luo2, Jungshan Chang4, Ai-Sheng Ho1
1Division of Gastroenterology, Cheng Hsin General Hospital, Taipei, Taiwan
2Institute of Nuclear Energy Research, Atomic Energy Council, Taoyuan, Taiwan
3Division of Proctology, Cheng Hsin General Hospital, Taipei, Taiwan
4Graduate Institute of Medical Sciences, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan

Tóm tắt

SummaryBackgroundStatins 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).MethodsPravastatin‐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).ResultsWe 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.ConclusionThis 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.

Tài liệu tham khảo

10.1136/gutjnl-2012-303000 Ren J.S., 2012, Estimation and prediction for incidence, mortality and prevalence of common gastrointestinal tract cancers in China, in 2008, Zhonghua Liu Xing Bing Xue Za Zhi, 33, 1052 Cheng C.C., 2013, Novel targeted nuclear imaging agent for gastric cancer diagnosis: glucose‐regulated protein 78 binding peptide‐guided (111)In‐labeled polymeric micelles, Int J Nanomedicine, 8, 1385, 10.2147/IJN.S42003 10.1002/pmic.201100602 Slater E.E., 1988, Mechanism of action and biological profile of HMG CoA reductase inhibitors. A new therapeutic alternative, Drugs, 36, 72, 10.2165/00003495-198800363-00016 10.1055/s-2003-37501 10.1111/j.1572-0241.2007.01773.x 10.1592/phco.30.2.169 10.1016/j.jconrel.2010.09.011 10.1016/S0021-9150(03)00094-7 10.1158/1535-7163.MCT-11-0905 10.1155/2011/496925 10.1161/01.RES.0000146094.59640.13 10.1161/ATVBAHA.109.200196 10.1073/pnas.1009010107 10.1074/jbc.M113.468967 10.1007/s11745-002-0981-4 Murphy A.J., 2010, Neutrophil activation is attenuated by high‐density lipoprotein and apolipoprotein A‐I in in vitro and in vivo models of inflammation, Arterioscler Thromb Vasc Biol, 31, 1333, 10.1161/ATVBAHA.111.226258 10.1155/2012/386395 10.1371/journal.pone.0028813 10.1016/j.jprot.2010.04.005 10.1186/1471-2407-10-103 10.1002/jat.1337 10.1186/1475-2867-12-5 Kamigaki M., 2011, Statins induce apoptosis and inhibit proliferation in cholangiocarcinoma cells, Int J Oncol, 39, 561 10.5551/jat.13532 10.1007/s002280050319 10.1016/j.lfs.2004.10.066 10.1002/pmic.200500093 10.1016/j.molonc.2012.03.005 10.1038/nm.2084 10.1186/1477-5956-9-21 10.1161/01.CIR.0000159351.95399.50 10.1177/1074248411434598
Thông tin
Thông tin xuất bản

ADVANCES IN DIGESTIVE MEDICINE

Tập 3

3-10

Thông tin tác giả