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dc.contributor.authorMohammadi, Ali
dc.contributor.authorMansoori, Behzad
dc.contributor.authorSavadi, Pouria
dc.contributor.authorKhaze, Vahid
dc.contributor.authorMinouei, Mahsa
dc.contributor.authorMcMillan, Nigel AJ
dc.contributor.authorHallaj-Nezhadi, Somayeh
dc.contributor.authorBaradaran, Behzad
dc.date.accessioned2019-06-09T01:34:03Z
dc.date.available2019-06-09T01:34:03Z
dc.date.issued2019
dc.identifier.issn0730-2312
dc.identifier.doi10.1002/jcb.28196
dc.identifier.urihttp://hdl.handle.net/10072/383515
dc.description.abstractBackground: Considering the complex nature of gastrointestinal cancer, different methods including surgery, radiotherapy, and chemotherapy are considered for the treatment. Novel strategies including silencing of oncogenes using safe delivery systems could be considered as a novel approach in colorectal cancer treatment. The aim of this study was to investigate the silencing effect of high mobility group A2 (HMGA2) small interfering RNA (siRNA)–loaded nanoliposomes on gastrointestinal cancers. Methods: The siRNA-lipoplexes were prepared using dioleoyl trimethylammonium propane (DOTAP)/cholesterol (Chol)/1, 2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) through the freeze-drying of a monophase solution method. The size, polydispersity index (PDI), and zeta-potential of nanoliposomes were determined using Zetasizer analyzer. The morphology of the nanoliposomes was determined by transmission electron microscopy (TEM). The agarose gel-retardation assay was carried out to confirm the loading of siRNAs into liposome. The silencing of the HMGA2 in cancer cells was evaluated by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). The effect of liposomes on cell cytotoxicity was studied by MTT assay. The inhibitory effect of siRNA-loaded liposomes was evaluated by a wound-healing assay. The apoptosis induction was investigated via the annexin V/propidium iodide assay. Results: The size, PDI, and zeta-potential of the prepared liposomes were found to be 350 nm, 0.67, and 86.3 mV, respectively. They were spherical in shape and could efficiently associate with siRNA. The results of gene silencing showed that the optimum condition of HMGA2 silencing was 80 pmol HMGA2 and 24 hours after treatment in each cancer cell lines. MTT assays indicated that silencing of HMGA2 in optimal condition could reduce the viability of the cancer cells more than 60% in the three cell lines. The result of the apoptosis assay showed more than 50% of the cell deaths related to the apoptosis in all three cell lines. The gene expression evaluation confirmed that apoptosis was induced via the intrinsic pathway inducing both caspase-3 and -9 expressions. Also, the reduction in Bcl2 expression confirmed the activation apoptosis pathway in the treated cancer cells. The wound-healing assay showed the suppression of cancer cell migration after treatment with the prepared nanoliposomes. Conclusion: The results of this study showed the HMGA2 siRNA-loaded nanoliposomes could be effective in the treatment of gastrointestinal cancers.
dc.description.peerreviewedYes
dc.languageEnglish
dc.language.isoeng
dc.publisherWILEY
dc.relation.ispartofpagefrom9203
dc.relation.ispartofpageto9212
dc.relation.ispartofissue6
dc.relation.ispartofjournalJOURNAL OF CELLULAR BIOCHEMISTRY
dc.relation.ispartofvolume120
dc.subject.fieldofresearchBiochemistry and cell biology
dc.subject.fieldofresearchMedical physiology
dc.subject.fieldofresearchcode3101
dc.subject.fieldofresearchcode3208
dc.titleTargeting of high mobility group A2 by small interfering RNA-loaded nanoliposome-induced apoptosis and migration inhibition in gastrointestinal cancer cells
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
gro.hasfulltextNo Full Text
gro.griffith.authorMcMillan, Nigel


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