{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T22:29:23Z","timestamp":1781821763738,"version":"3.54.5"},"reference-count":47,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2018,8,1]],"date-time":"2018-08-01T00:00:00Z","timestamp":1533081600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2018,8,1]],"date-time":"2018-08-01T00:00:00Z","timestamp":1533081600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"funder":[{"name":"Natural Science Basic Research Plan in Shaanxi Province of China","award":["2016JQ8036"],"award-info":[{"award-number":["2016JQ8036"]}]},{"name":"Science Foundation of First Affiliated Hospital of Xi\u2019an Jiaotong University","award":["YK201518"],"award-info":[{"award-number":["YK201518"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81702434"],"award-info":[{"award-number":["81702434"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["The International Journal of Biochemistry &amp; Cell Biology"],"published-print":{"date-parts":[[2018,8]]},"DOI":"10.1016\/j.biocel.2018.05.013","type":"journal-article","created":{"date-parts":[[2018,5,22]],"date-time":"2018-05-22T12:46:26Z","timestamp":1526993186000},"page":"39-48","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":32,"special_numbering":"C","title":["MEL-pep, an analog of melittin, disrupts cell membranes and reverses 5-fluorouracil resistance in human hepatocellular carcinoma cells"],"prefix":"10.1016","volume":"101","author":[{"given":"Mengyun","family":"Ke","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Lv","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rongqian","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.biocel.2018.05.013_bib0005","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.jare.2014.11.008","article-title":"P-glycoprotein inhibitors of natural origin as potential tumor chemo-sensitizers: a review","volume":"6","author":"Abdallah","year":"2015","journal-title":"J. Adv. Res."},{"key":"10.1016\/j.biocel.2018.05.013_bib0010","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1016\/j.ejps.2006.08.006","article-title":"LY294,002, a specific inhibitor of PI3K\/Akt kinase pathway, antagonizes P-glycoprotein-mediated multidrug resistance","volume":"29","author":"Barancik","year":"2006","journal-title":"Eur. J. Pharm. Sci."},{"key":"10.1016\/j.biocel.2018.05.013_bib0015","doi-asserted-by":"crossref","first-page":"3809","DOI":"10.1007\/s00018-017-2604-z","article-title":"Tumor cell membrane-targeting cationic antimicrobial peptides: novel insights into mechanisms of action and therapeutic prospects","volume":"74","author":"Baxter","year":"2017","journal-title":"Cell. Mol. Life Sci."},{"key":"10.1016\/j.biocel.2018.05.013_bib0020","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.biochi.2016.01.014","article-title":"Nelfinavir targets multiple drug resistance mechanisms to increase the efficacy of doxorubicin in MCF-7\/Dox breast cancer cells","volume":"124","author":"Chakravarty","year":"2016","journal-title":"Biochimie"},{"key":"10.1016\/j.biocel.2018.05.013_bib0025","doi-asserted-by":"crossref","first-page":"6483","DOI":"10.3892\/mmr.2015.4275","article-title":"Melittin, a honeybee venomderived antimicrobial peptide, may target methicillinresistant Staphylococcus aureus","volume":"12","author":"Choi","year":"2015","journal-title":"Mol. Med. Rep."},{"key":"10.1016\/j.biocel.2018.05.013_bib0030","doi-asserted-by":"crossref","first-page":"46635","DOI":"10.18632\/oncotarget.16743","article-title":"Antimicrobial peptides with selective antitumor mechanisms: prospect for anticancer applications","volume":"8","author":"Deslouches","year":"2017","journal-title":"Oncotarget"},{"key":"10.1016\/j.biocel.2018.05.013_bib0035","doi-asserted-by":"crossref","first-page":"2824","DOI":"10.1002\/cncr.28730","article-title":"The clinical management of hepatocellular carcinoma in the United States, Europe, and Asia: a comprehensive and evidence-based comparison and review","volume":"120","author":"Fong","year":"2014","journal-title":"Cancer"},{"key":"10.1016\/j.biocel.2018.05.013_bib0040","first-page":"493","article-title":"Tumor-specific targeting by Bavituximab, a phosphatidylserine-targeting monoclonal antibody with vascular targeting and immune modulating properties, in lung cancer xenografts","volume":"5","author":"Gerber","year":"2015","journal-title":"Am. J. Nucl. Med. Mol. Imaging"},{"key":"10.1016\/j.biocel.2018.05.013_bib0045","doi-asserted-by":"crossref","first-page":"205","DOI":"10.3389\/fphar.2017.00205","article-title":"Mechanism underlying the reversal of drug resistance in P-glycoprotein-expressing leukemia cells by pinoresinol and the study of a derivative","volume":"8","author":"Gonzalez","year":"2017","journal-title":"Front. Pharmacol."},{"key":"10.1016\/j.biocel.2018.05.013_bib0050","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/0160-9327(88)90082-8","article-title":"Honeybee venom: a rich source of pharmacologically active peptides","volume":"12","author":"Hider","year":"1988","journal-title":"Endeavour"},{"key":"10.1016\/j.biocel.2018.05.013_bib0055","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.1016\/j.bcp.2013.02.005","article-title":"Parguerenes: marine red alga bromoditerpenes as inhibitors of P-glycoprotein (ABCB1) in multidrug resistant human cancer cells","volume":"85","author":"Huang","year":"2013","journal-title":"Biochem. Pharmacol."},{"key":"10.1016\/j.biocel.2018.05.013_bib0060","doi-asserted-by":"crossref","DOI":"10.1155\/2014\/978034","article-title":"Panaxatriol saponins attenuated oxygen-glucose deprivation injury in PC12 cells via activation of PI3K\/Akt and Nrf2 signaling pathway","volume":"2014","author":"Huang","year":"2014","journal-title":"Oxid. Med. Cell. Longev."},{"key":"10.1016\/j.biocel.2018.05.013_bib0065","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.canlet.2017.03.015","article-title":"The dopamine D3 receptor antagonists PG01037, NGB2904, SB277011A, and U99194 reverse ABCG2 transporter-mediated drug resistance in cancer cell lines","volume":"396","author":"Hussein","year":"2017","journal-title":"Cancer Lett."},{"key":"10.1016\/j.biocel.2018.05.013_bib0070","doi-asserted-by":"crossref","first-page":"1729","DOI":"10.1248\/bpb.b12-00371","article-title":"Effects of Kampo medicines on MDR-1-mediated multidrug resistance in human hepatocellular carcinoma HuH-7\/PTX cells","volume":"35","author":"Hyuga","year":"2012","journal-title":"Biol. Pharm. Bull."},{"key":"10.1016\/j.biocel.2018.05.013_bib0075","doi-asserted-by":"crossref","first-page":"610","DOI":"10.3389\/fphar.2017.00610","article-title":"Exhibits similar cytostatic effect in drug-resistant and drug-sensitive multiple myeloma cells","volume":"8","author":"Issa","year":"2017","journal-title":"Front. Pharmacol."},{"key":"10.1016\/j.biocel.2018.05.013_bib0080","doi-asserted-by":"crossref","first-page":"40","DOI":"10.2174\/1568026615666150703115919","article-title":"Model membrane and cell studies of antimicrobial activity of melittin analogues","volume":"16","author":"Jamasbi","year":"2016","journal-title":"Curr. Top. Med. Chem."},{"key":"10.1016\/j.biocel.2018.05.013_bib0085","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1016\/j.fct.2014.03.022","article-title":"Melittin suppresses EGF-induced cell motility and invasion by inhibiting PI3K\/Akt\/mTOR signaling pathway in breast cancer cells","volume":"68","author":"Jeong","year":"2014","journal-title":"Food Chem. Toxicol."},{"key":"10.1016\/j.biocel.2018.05.013_bib0090","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.taap.2011.10.009","article-title":"Anti-cancer effect of bee venom toxin and melittin in ovarian cancer cells through induction of death receptors and inhibition of JAK2\/STAT3 pathway","volume":"258","author":"Jo","year":"2012","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"10.1016\/j.biocel.2018.05.013_bib0095","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1111\/j.1476-5381.2010.01101.x","article-title":"Metformin inhibits P-glycoprotein expression via the NF-kappaB pathway and CRE transcriptional activity through AMPK activation","volume":"162","author":"Kim","year":"2011","journal-title":"Br. J. Pharmacol."},{"key":"10.1016\/j.biocel.2018.05.013_bib0100","doi-asserted-by":"crossref","first-page":"3186","DOI":"10.3748\/wjg.v22.i11.3186","article-title":"Melittin induces human gastric cancer cell apoptosis via activation of mitochondrial pathway","volume":"22","author":"Kong","year":"2016","journal-title":"World J. Gastroenterol."},{"key":"10.1016\/j.biocel.2018.05.013_bib0105","doi-asserted-by":"crossref","first-page":"1945","DOI":"10.1038\/sj.onc.1205117","article-title":"Induction of human MDR1 gene expression by 2-acetylaminofluorene is mediated by effectors of the phosphoinositide 3-kinase pathway that activate NF-kappaB signaling","volume":"21","author":"Kuo","year":"2002","journal-title":"Oncogene"},{"key":"10.1016\/j.biocel.2018.05.013_bib0110","doi-asserted-by":"crossref","first-page":"54951","DOI":"10.18632\/oncotarget.18627","article-title":"Melittin suppresses tumor progression by regulating tumor-associated macrophages in a Lewis lung carcinoma mouse model","volume":"8","author":"Lee","year":"2017","journal-title":"Oncotarget"},{"key":"10.1016\/j.biocel.2018.05.013_bib0115","doi-asserted-by":"crossref","first-page":"11547","DOI":"10.18632\/oncotarget.3413","article-title":"Epigenetic silencing of BCL6B inactivates p53 signaling and causes human hepatocellular carcinoma cell resist to 5-FU","volume":"6","author":"Li","year":"2015","journal-title":"Oncotarget"},{"key":"10.1016\/j.biocel.2018.05.013_bib0120","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1007\/s11255-015-1155-1","article-title":"Externalization of phosphatidylserine via multidrug resistance 1 (MDR1)\/P-glycoprotein in oxalate-treated renal epithelial cells: implications for calcium oxalate urolithiasis","volume":"48","author":"Li","year":"2016","journal-title":"Int. Urol. Nephrol."},{"issue":"Suppl","key":"10.1016\/j.biocel.2018.05.013_bib0125","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.1007\/s002800051053","article-title":"Multidrug resistance: molecular mechanisms and clinical relevance","volume":"40","author":"Ling","year":"1997","journal-title":"Cancer Chemother. Pharmacol."},{"key":"10.1016\/j.biocel.2018.05.013_bib0130","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1007\/s00280-016-3160-1","article-title":"Application of bee venom and its main constituent melittin for cancer treatment","volume":"78","author":"Liu","year":"2016","journal-title":"Cancer Chemother. Pharmacol."},{"key":"10.1016\/j.biocel.2018.05.013_bib0135","doi-asserted-by":"crossref","first-page":"1964","DOI":"10.1002\/hep.22240","article-title":"Melittin prevents liver cancer cell metastasis through inhibition of the Rac1-dependent pathway","volume":"47","author":"Liu","year":"2008","journal-title":"Hepatology (Baltimore, Md.)"},{"key":"10.1016\/j.biocel.2018.05.013_bib0140","doi-asserted-by":"crossref","first-page":"1092","DOI":"10.1016\/j.intimp.2007.04.005","article-title":"Bee venom and melittin reduce proinflammatory mediators in lipopolysaccharide-stimulated BV2 microglia","volume":"7","author":"Moon","year":"2007","journal-title":"Int. Immunopharmacol."},{"key":"10.1016\/j.biocel.2018.05.013_bib0145","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1177\/1534735411413265","article-title":"Effects of sweet bee venom pharmacopuncture treatment for chemotherapy-induced peripheral neuropathy: a case series","volume":"11","author":"Park","year":"2012","journal-title":"Integr. Cancer Ther."},{"key":"10.1016\/j.biocel.2018.05.013_bib0150","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.canlet.2017.05.010","article-title":"Melittin, a major peptide component of bee venom, and its conjugates in cancer therapy","volume":"402","author":"Rady","year":"2017","journal-title":"Cancer Lett."},{"key":"10.1016\/j.biocel.2018.05.013_bib0155","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1038\/316817a0","article-title":"Amplification of P-glycoprotein genes in multidrug-resistant mammalian cell lines","volume":"316","author":"Riordan","year":"1985","journal-title":"Nature"},{"key":"10.1016\/j.biocel.2018.05.013_bib0160","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0056197","article-title":"Identification of the genes chemosensitizing hepatocellular carcinoma cells to interferon-alpha\/5-fluorouracil and their clinical significance","volume":"8","author":"Sakabe","year":"2013","journal-title":"PLoS One"},{"key":"10.1016\/j.biocel.2018.05.013_bib0165","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1002\/emmm.201101131","article-title":"Role of intratumoural heterogeneity in cancer drug resistance: molecular and clinical perspectives","volume":"4","author":"Saunders","year":"2012","journal-title":"EMBO Mol. Med."},{"key":"10.1016\/j.biocel.2018.05.013_bib0170","doi-asserted-by":"crossref","first-page":"2466","DOI":"10.1111\/liv.12844","article-title":"TRIP: a pathological score for transarterial chemoembolization resistance individualized prediction in hepatocellular carcinoma","volume":"35","author":"Sciarra","year":"2015","journal-title":"Liver Int."},{"key":"10.1016\/j.biocel.2018.05.013_bib0175","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.canlet.2008.04.033","article-title":"Reversal effect of tyroservatide (YSV) tripeptide on multi-drug resistance in resistant human hepatocellular carcinoma cell line BEL-7402\/5-FU","volume":"269","author":"Shi","year":"2008","journal-title":"Cancer Lett."},{"key":"10.1016\/j.biocel.2018.05.013_bib0180","doi-asserted-by":"crossref","DOI":"10.1007\/s40268-017-0187-7","article-title":"A phase I study of combination therapy with sorafenib and 5-fluorouracil in patients with advanced hepatocellular carcinoma","author":"Sho","year":"2017","journal-title":"Drugs R D"},{"key":"10.1016\/j.biocel.2018.05.013_bib0185","doi-asserted-by":"crossref","first-page":"7024","DOI":"10.1073\/pnas.95.12.7024","article-title":"The drug efflux protein, P-glycoprotein, additionally protects drug-resistant tumor cells from multiple forms of caspase-dependent apoptosis","volume":"95","author":"Smyth","year":"1998","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"10.1016\/j.biocel.2018.05.013_bib0190","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1038\/nature13176","article-title":"Identification of genomic alterations in oesophageal squamous cell cancer","volume":"509","author":"Song","year":"2014","journal-title":"Nature"},{"key":"10.1016\/j.biocel.2018.05.013_bib0195","doi-asserted-by":"crossref","first-page":"6010","DOI":"10.1016\/S0021-9258(20)65097-9","article-title":"The structure of melittin. I. Structure determination and partial refinement","volume":"257","author":"Terwilliger","year":"1982","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.biocel.2018.05.013_bib0200","doi-asserted-by":"crossref","first-page":"1887","DOI":"10.1074\/jbc.275.3.1887","article-title":"Up-regulation of multidrug resistance P-glycoprotein via nuclear factor-kappaB activation protects kidney proximal tubule cells from cadmium- and reactive oxygen species-induced apoptosis","volume":"275","author":"Thevenod","year":"2000","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.biocel.2018.05.013_bib0205","first-page":"87","article-title":"Global cancer statistics, 2012","volume":"65","author":"Torre","year":"2015","journal-title":"CA Cancer J. Clin."},{"key":"10.1016\/j.biocel.2018.05.013_bib0210","first-page":"3062","article-title":"Elevated expression of phosphatidylserine in the outer membrane leaflet of human tumor cells and recognition by activated human blood monocytes","volume":"51","author":"Utsugi","year":"1991","journal-title":"Cancer Res."},{"key":"10.1016\/j.biocel.2018.05.013_bib0215","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.canlet.2017.04.012","article-title":"Melittin inhibits tumor growth and decreases resistance to gemcitabine by downregulating cholesterol pathway gene CLU in pancreatic ductal adenocarcinoma","volume":"399","author":"Wang","year":"2017","journal-title":"Cancer Lett."},{"key":"10.1016\/j.biocel.2018.05.013_bib0220","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.taap.2015.07.010","article-title":"Melittin induces PTCH1 expression by down-regulating MeCP2 in human hepatocellular carcinoma SMMC-7721 cells","volume":"288","author":"Wu","year":"2015","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"10.1016\/j.biocel.2018.05.013_bib0225","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1080\/15476278.2016.1185584","article-title":"Decellularized spleen matrix for reengineering functional hepatic-like tissue based on bone marrow mesenchymal stem cells","volume":"12","author":"Xiang","year":"2016","journal-title":"Organogenesis"},{"key":"10.1016\/j.biocel.2018.05.013_bib0230","article-title":"An update on circumventing multidrug resistance in cancer by targeting P-glycoprotein","author":"Yang","year":"2017","journal-title":"Curr. Cancer Drug Targets"},{"key":"10.1016\/j.biocel.2018.05.013_bib0235","doi-asserted-by":"crossref","first-page":"1526","DOI":"10.1016\/j.xphs.2016.01.020","article-title":"Effects of polyoxyethylene alkyl ethers on the intestinal transport and absorption of rhodamine 123: a P-glycoprotein substrate by in vitro and in vivo studies","volume":"105","author":"Zhao","year":"2016","journal-title":"J. Pharm. Sci."}],"container-title":["The International Journal of Biochemistry &amp; Cell Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1357272518301250?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1357272518301250?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T07:13:00Z","timestamp":1761203580000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1357272518301250"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,8]]},"references-count":47,"alternative-id":["S1357272518301250"],"URL":"https:\/\/doi.org\/10.1016\/j.biocel.2018.05.013","relation":{},"ISSN":["1357-2725"],"issn-type":[{"value":"1357-2725","type":"print"}],"subject":[],"published":{"date-parts":[[2018,8]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"MEL-pep, an analog of melittin, disrupts cell membranes and reverses 5-fluorouracil resistance in human hepatocellular carcinoma cells","name":"articletitle","label":"Article Title"},{"value":"The International Journal of Biochemistry & Cell Biology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.biocel.2018.05.013","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2018 Elsevier Ltd. All rights reserved.","name":"copyright","label":"Copyright"}]}}