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Antitumor Effects Of Curcumin Combined With Bcr/abl Antisense Oligodeoxynucleotides On Chronic Myelogenous Leukemia Cell Line K562

Posted on:2005-01-19Degree:MasterType:Thesis
Country:ChinaCandidate:K Z ZhangFull Text:PDF
GTID:2144360125960786Subject:Pharmacology
Abstract/Summary:PDF Full Text Request
Objective To study the antitumor effects of Curcumin(Cur) combined with bcr/abl antisense Oligodeoxynucleotides(ASODN) on Chronic Myelogenous Leukemia(CML)cell line K562 and to explore its antitumour characters and mechanism .Methods P210bcr/abl positive cell line K562 was used as a model. Thus phosphorothioate antisense oligodeoxynucleotides was used to evaluate how Cur induced apoptosis and inhibition on K562 cells after bcr/abl mRNA was blocked; AO/EB fluoresent staining and MTT assay were used to determine the apoptosis and proliferation on K562 cells after treated with Cur and ASODN; Western blot was used to analyse the downregulation of P210bcr/abl protein and its activated downstream signals after treated with Cur and ASODN.Results 1, ASODN had an effect on K562 cells, the inhibition was significant after treating 72 hours, and showed dose- and time- dependent manner; while treating 120h ,its inhibitory effect was at the state of plateau. 2, AO/EB fluoresent staining showed higher apoptotic rate induced by Cur combined with ASODN than Cur treated alone. 3, MTT assay showed Cur had higher inhibitory rate combined with ASODN than Cur treated alone. The results showed that Cur had significant synergism with ASODN when bcr/abl mRNA was preferentially blocked. 4, Western blot showed from molecular mechanism that Cur could downregulate P210bcr/abl protein with time- and dose-dependent manner, it progressively indicated that Cur combined with ASODN downregulated P210bcr/abl protein more significantly than Cur treated alone. And this also reflected the correspondence of its downregulation of NF-КB—the downstream apoptotic signal of P210bcr/ablprotein. Conclusion Cur combined with ASODN took Synergetic effects of apoptosis and inhibition on K562 cells and the correspondence of its downregulation of P210bcr/abl protein and its activated downstream signal -NF-КB , further indicated that Cur might have multi-targets of inducing inhibition and apoptosis on K562 cells of CML .
Keywords/Search Tags:Curcumin(Cur), Antisense Oligodeoxynucleotides(ASODN), Chronic Myelogenous Leukemia (CML), bcr/abl, P210bcr/abl Protein, Apoptosis, Singnal Transduction Pathway
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