{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T10:52:37Z","timestamp":1776423157038,"version":"3.51.2"},"reference-count":61,"publisher":"Baishideng Publishing Group Inc.","issue":"32","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["WJG"],"published-print":{"date-parts":[[2016]]},"DOI":"10.3748\/wjg.v22.i32.7342","type":"journal-article","created":{"date-parts":[[2016,8,24]],"date-time":"2016-08-24T08:49:24Z","timestamp":1472028564000},"page":"7342","source":"Crossref","is-referenced-by-count":17,"title":["Synergistic anticancer effect of exogenous wild-type<i>p53<\/i>gene combined with 5-FU in human colon cancer resistant to 5-FU<i>in vivo<\/i>"],"prefix":"10.3748","volume":"22","author":[{"given":"Qi","family":"Xie","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min-Yi","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ding-Xuan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi-Ming","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bao-Shuai","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei-De","family":"Zhong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jia-Ni","family":"Hu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"2060","reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2015.0735"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.2010.03892.x"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1038\/srep04694"},{"key":"ref4","doi-asserted-by":"crossref","unstructured":"Sun XX, Dai MS, Lu H. 5-fluorouracil activation of p53 involves an MDM2-ribosomal protein interaction. J Biol Chem 2007;282:8052-8059.","DOI":"10.1074\/jbc.M610621200"},{"key":"ref5","unstructured":"Subbarayan PR, Sarkar M, Nelson G, Benitez E, Singhal S, Ardalan B. Chronic exposure of colorectal cancer cells in culture to fluoropyrimidine analogs induces thymidylate synthase and suppresses p53. A molecular explanation for the mechanism of 5-FU resistance. Anticancer Res 2010;30:1149-1156."},{"key":"ref6","doi-asserted-by":"crossref","unstructured":"Huang C, Zhang XM, Tavaluc RT, Hart LS, Dicker DT, Wang W, El-Deiry WS. The combination of 5-fluorouracil plus p53 pathway restoration is associated with depletion of p53-deficient or mutant p53-expressing putative colon cancer stem cells. Cancer Biol Ther 2009;8:2186-2193.","DOI":"10.4161\/cbt.8.22.10446"},{"key":"ref7","doi-asserted-by":"crossref","unstructured":"Baek JH, Agarwal ML, Tubbs RR, Vladisavljevic A, Tomita H, Bukowski RM, Milsom JW, Kim JM, Kwak JY. In vivo recombinant adenovirus-mediated p53 gene therapy in a syngeneic rat model for colorectal cancer. J Korean Med Sci 2004;19:834-841.","DOI":"10.3346\/jkms.2004.19.6.834"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.3748\/WJG.v13.i7.985"},{"key":"ref9","doi-asserted-by":"crossref","unstructured":"Inoue H, Shiraki K, Murata K, Sugimoto K, Kawakita T, Yamaguchi Y, Saitou Y, Enokimura N, Yamamoto N, Yamanaka Y. Adenoviral-mediated transfer of p53 gene enhances TRAIL-induced apoptosis in human hepatocellular carcinoma cells. Int J Mol Med 2004;14:271-275.","DOI":"10.3892\/ijmm.14.2.271"},{"key":"ref10","doi-asserted-by":"crossref","unstructured":"Roth JA. Adenovirus p53 gene therapy. Expert Opin Biol Ther 2006;6:55-61.","DOI":"10.1517\/14712598.6.1.55"},{"key":"ref11","doi-asserted-by":"crossref","unstructured":"Shimada H, Shimizu T, Ochiai T, Liu TL, Sashiyama H, Nakamura A, Matsubara H, Gunji Y, Kobayashi S, Tagawa M. Preclinical study of adenoviral p53 gene therapy for esophageal cancer. Surg Today 2001;31:597-604.","DOI":"10.1007\/s005950170093"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v17.i38.4289"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2012.02.007"},{"key":"ref14","unstructured":"Xie Q, Yang YM, Wu MYi, Zhang DX, Lei ZX, Zhang J, Xu J, Zhong WD. Detection of the drug resistance of human colon cancer in mice with magnetic resonance diffusion imaging. ZhongguoLinchuangYixueYingxiangZazhi 2016;17:355-358, 366."},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.5327"},{"key":"ref16","doi-asserted-by":"crossref","unstructured":"Zhang N, Yin Y, Xu SJ, Chen WS. 5-Fluorouracil: mechanisms of resistance and reversal strategies. Molecules 2008;13:1551-1569.","DOI":"10.3390\/molecules13081551"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1016\/j.drup.2014.11.002"},{"key":"ref18","doi-asserted-by":"crossref","unstructured":"Michaelis M, Rothweiler F, L&ouml;schmann N, Sharifi M, Ghafourian T, Cinatl J. Enzastaurin inhibits ABCB1-mediated drug efflux independently of effects on protein kinase C signalling and the cellular p53 status. Oncotarget 2015;6:17605-17620.","DOI":"10.18632\/oncotarget.2889"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.1007\/s00384-010-0961-2"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.1111\/j.1463-1318.2012.02919.x"},{"key":"ref21","doi-asserted-by":"crossref","unstructured":"Wang X, Wang C, Qin YW, Yan SK, Gao YR. Simultaneous suppression of multidrug resistance and antiapoptotic cellular defense induces apoptosis in chemoresistant human acute myeloid leukemia cells. Leuk Res 2007;31:989-994.","DOI":"10.1016\/j.leukres.2006.09.001"},{"key":"ref22","doi-asserted-by":"crossref","unstructured":"O&rsquo;Brian CA, Ward NE, Stewart JR, Chu F. Prospects for targeting protein kinase C isozymes in the therapy of drug-resistant cancer--an evolving story. Cancer Metastasis Rev 2001;20:95-100.","DOI":"10.1023\/A:1013186430906"},{"key":"ref23","doi-asserted-by":"crossref","unstructured":"Zhan M, Yu D, Liu J, Glazer RI, Hannay J, Pollock RE. Transcriptional repression of protein kinase Calpha via Sp1 by wild type p53 is involved in inhibition of multidrug resistance 1 P-glycoprotein phosphorylation. J Biol Chem 2005;280:4825-4833.","DOI":"10.1074\/jbc.M407450200"},{"key":"ref24","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0090180"},{"key":"ref25","doi-asserted-by":"crossref","unstructured":"Xue C, Wang C, Liu Q, Meng Q, Sun H, Huo X, Ma X, Liu Z, Ma X, Peng J. Targeting P-glycoprotein expression and cancer cell energy metabolism: combination of metformin and 2-deoxyglucose reverses the multidrug resistance of K562\/Dox cells to doxorubicin. Tumour Biol 2016; Epub ahead of print.","DOI":"10.1007\/s13277-015-4478-8"},{"key":"ref26","doi-asserted-by":"publisher","DOI":"10.1016\/j.jare.2014.11.008"},{"key":"ref27","doi-asserted-by":"crossref","unstructured":"Kobori T, Harada S, Nakamoto K, Tokuyama S. Mechanisms of P-glycoprotein alteration during anticancer treatment: role in the pharmacokinetic and pharmacological effects of various substrate drugs. J Pharmacol Sci 2014;125:242-254.","DOI":"10.1254\/jphs.14R01CR"},{"key":"ref28","doi-asserted-by":"crossref","unstructured":"Gopalakrishna R, Gundimeda U. Antioxidant regulation of protein kinase C in cancer prevention. J Nutr 2002;132:3819S-3823S.","DOI":"10.1093\/jn\/132.12.3819S"},{"key":"ref29","doi-asserted-by":"publisher","DOI":"10.1021\/cb900258z"},{"key":"ref30","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2009.28"},{"key":"ref31","doi-asserted-by":"crossref","unstructured":"Caino MC, Meshki J, Kazanietz MG. Hallmarks for senescence in carcinogenesis: novel signaling players. Apoptosis 2009;14:392-408.","DOI":"10.1007\/s10495-009-0316-z"},{"key":"ref32","doi-asserted-by":"publisher","DOI":"10.1080\/01635581.2015.990574"},{"key":"ref33","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2882"},{"key":"ref34","doi-asserted-by":"crossref","unstructured":"Maurya AK, Vinayak M. Anticarcinogenic action of quercetin by downregulation of phosphatidylinositol 3-kinase (PI3K) and protein kinase C (PKC) via induction of p53 in hepatocellular carcinoma (HepG2) cell line. Mol Biol Rep 2015;42:1419-1429.","DOI":"10.1007\/s11033-015-3921-7"},{"key":"ref35","doi-asserted-by":"crossref","unstructured":"Geering B, Cutillas PR, Nock G, Gharbi SI, Vanhaesebroeck B. Class IA phosphoinositide 3-kinases are obligate p85-p110 heterodimers. Proc Natl Acad Sci USA 2007;104:7809-7814.","DOI":"10.1073\/pnas.0700373104"},{"key":"ref36","doi-asserted-by":"crossref","unstructured":"Masanek U, Stammler G, Volm M. Modulation of multidrug resistance in human ovarian cancer cell lines by inhibition of P-glycoprotein 170 and PKC isoenzymes with antisense oligonucleotides. J Exp Ther Oncol 2002;2:37-41.","DOI":"10.1046\/j.1359-4117.2002.01004.x"},{"key":"ref37","doi-asserted-by":"crossref","unstructured":"Carson DA, Lois A. Cancer progression and p53. Lancet 1995;346:1009-1011.","DOI":"10.1016\/S0140-6736(95)91693-8"},{"key":"ref38","doi-asserted-by":"publisher","DOI":"10.1016\/j.acthis.2012.08.001"},{"key":"ref39","unstructured":"Bookstein R, Demers W, Gregory R, Maneval D, Park J, Wills K. p53 gene therapy in vivo of herpatocellular and liver metastatic colorectal cancer. Semin Oncol 1996;23:66-77."},{"key":"ref40","doi-asserted-by":"crossref","unstructured":"Hollstein M, Sidransky D, Vogelstein B, Harris CC. p53 mutations in human cancers. Science 1991;253:49-53.","DOI":"10.1126\/science.1905840"},{"key":"ref41","doi-asserted-by":"crossref","unstructured":"Levine AJ, Momand J, Finlay CA. The p53 tumour suppressor gene. Nature 1991;351:453-456.","DOI":"10.1038\/351453a0"},{"key":"ref42","unstructured":"Spitz FR, Nguyen D, Skibber JM, Cusack J, Roth JA, Cristiano RJ. In vivo adenovirus-mediated p53 tumor suppressor gene therapy for colorectal cancer. Anticancer Res 1996;16:3415-3422."},{"key":"ref43","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-394274-6.00003-0"},{"key":"ref44","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-12-3289"},{"key":"ref45","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2693"},{"key":"ref46","doi-asserted-by":"crossref","unstructured":"Olivier M, Langer&oslash;d A, Carrieri P, Bergh J, Klaar S, Eyfjord J, Theillet C, Rodriguez C, Lidereau R, Bi&egrave;che I. The clinical value of somatic TP53 gene mutations in 1,794 patients with breast cancer. Clin Cancer Res 2006;12:1157-1167.","DOI":"10.1158\/1078-0432.CCR-05-1029"},{"key":"ref47","doi-asserted-by":"publisher","DOI":"10.1097\/CAD.0b013e328345b4e7"},{"key":"ref48","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0023887"},{"key":"ref49","doi-asserted-by":"crossref","unstructured":"Levine AJ. p53, the cellular gatekeeper for growth and division. Cell 1997;88:323-331.","DOI":"10.1016\/S0092-8674(00)81871-1"},{"key":"ref50","doi-asserted-by":"crossref","unstructured":"Ko LJ, Prives C. p53: puzzle and paradigm. Genes Dev 1996;10:1054-1072.","DOI":"10.1101\/gad.10.9.1054"},{"key":"ref51","doi-asserted-by":"crossref","unstructured":"Vogelstein B, Kinzler KW. p53 function and dysfunction. Cell 1992;70:523-526.","DOI":"10.1016\/0092-8674(92)90421-8"},{"key":"ref52","doi-asserted-by":"crossref","unstructured":"Haupt Y, Maya R, Kazaz A, Oren M. Mdm2 promotes the rapid degradation of p53. Nature 1997;387:296-299.","DOI":"10.1038\/387296a0"},{"key":"ref53","doi-asserted-by":"crossref","unstructured":"Kubbutat MH, Jones SN, Vousden KH. Regulation of p53 stability by Mdm2. Nature 1997;387:299-303.","DOI":"10.1038\/387299a0"},{"key":"ref54","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0110844"},{"key":"ref55","doi-asserted-by":"crossref","unstructured":"Linke SP, Clarkin KC, Di Leonardo A, Tsou A, Wahl GM. A reversible, p53-dependent G0\/G1 cell cycle arrest induced by ribonucleotide depletion in the absence of detectable DNA damage. Genes Dev 1996;10:934-947.","DOI":"10.1101\/gad.10.8.934"},{"key":"ref56","doi-asserted-by":"crossref","unstructured":"Mowat MR. p53 in tumor progression: life, death, and everything. Adv Cancer Res 1998;74:25-48.","DOI":"10.1016\/S0065-230X(08)60764-2"},{"key":"ref57","doi-asserted-by":"crossref","unstructured":"Shaw P, Bovey R, Tardy S, Sahli R, Sordat B, Costa J. Induction of apoptosis by wild-type p53 in a human colon tumor-derived cell line. Proc Natl Acad Sci USA 1992;89:4495-4499.","DOI":"10.1073\/pnas.89.10.4495"},{"key":"ref58","doi-asserted-by":"crossref","unstructured":"Yonish-Rouach E, Resnitzky D, Lotem J, Sachs L, Kimchi A, Oren M. Wild-type p53 induces apoptosis of myeloid leukaemic cells that is inhibited by interleukin-6. Nature 1991;352:345-347.","DOI":"10.1038\/352345a0"},{"key":"ref59","doi-asserted-by":"crossref","unstructured":"Ju J, Schmitz JC, Song B, Kudo K, Chu E. Regulation of p53 expression in response to 5-fluorouracil in human cancer RKO cells. Clin Cancer Res 2007;13:4245-4251.","DOI":"10.1158\/1078-0432.CCR-06-2890"},{"key":"ref60","doi-asserted-by":"publisher","DOI":"10.1007\/s10495-013-0907-6"},{"key":"ref61","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-09-0912"}],"container-title":["World Journal of Gastroenterology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.wjgnet.com\/1007-9327\/full\/v22\/i32\/7342.htm","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,9,12]],"date-time":"2019-09-12T22:32:30Z","timestamp":1568327550000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.wjgnet.com\/1007-9327\/full\/v22\/i32\/7342.htm"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016]]},"references-count":61,"journal-issue":{"issue":"32","published-print":{"date-parts":[[2016]]}},"URL":"https:\/\/doi.org\/10.3748\/wjg.v22.i32.7342","relation":{},"ISSN":["1007-9327"],"issn-type":[{"value":"1007-9327","type":"print"}],"subject":[],"published":{"date-parts":[[2016]]}}}