title: Tankyrase 1 inhibitior XAV939 increases chemosensitivity in colon cancer cell lines via inhibition of the Wnt signaling pathway.
abstract: Aberrant Wnt signaling pathway is associated with a wide array of tumor types and plays an important role in the drug resistance of cancer stem cells (CSCs). To explore the effects and mechanism of WNT signaling pathway inhibitor XAV939 on drug resistance in colon cancer cells, the colon cancer cells SW480 and SW620 were treated with 5-fluorouracil (5-FU)/cisplatin (DDP) alone or combined with XAV939. Cell cycle distribution, apoptosis level and the percentage of CD133+ cells were detected by flow cytometry. The protein expression of Axin, β-catenin, EpCAM, TERT and DCAMKL-1 was detected by western blotting. XAV939 upregulated Axin , decreased the total and nuclei of β-catenin in SW480 and SW620 cells. Furthermore, XAV939 significantly downregulated the CSC markers EpCAM, TERT and DCAMKL-1 in SW480 cells, as well as EpCAM in SW620 cells. No significant difference was found in the apoptosis of SW480 and SW620 cells with XAV939 treatment, but XAV939 significantly increased apoptosis induced by 5-FU/DDP in SW480 cells, whereas, the effects were slight in SW620 cells. Collectively, we show for the first time that the WNT signaling pathway inhibitor XAV939 was able to significantly increase the apoptosis induced by 5-FU/DDP, accompanied by the protein expression level alternation of β-catenin, Axin and CSC markers in colon cancer cells. Axin, an important component of Wnt/β-catenin signaling pathway could be a potential molecular target for reversing multidrug resistance in colon cancer.
authors.affiliation: Department of Pathology, Qingyuan People's Hospital, Jinan University, Qingyuan, Guangdong 511518, P.R. China.
authors.forename: Xuefang
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Pathology, Qingyuan People's Hospital, Jinan University, Qingyuan, Guangdong 511518, P.R. China.
authors.forename: Feng
authors.initials: F
authors.lastname: Luo
authors.affiliation: Department of Pathology, Qingyuan People's Hospital, Jinan University, Qingyuan, Guangdong 511518, P.R. China.
authors.forename: Jinbang
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Pathology, Medical College, Jinan University, Guangzhou, Guangdong 510632, P.R. China.
authors.forename: Xueyun
authors.initials: X
authors.lastname: Zhong
authors.affiliation: Department of Pathology, Qingyuan People's Hospital, Jinan University, Qingyuan, Guangdong 511518, P.R. China.
authors.forename: Kunping
authors.initials: K
authors.lastname: Liu
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D060466:Axin Protein / Q000096:biosynthesis* / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005472:Fluorouracil / Q000008:administration & dosage; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006575:Heterocyclic Compounds, 3-Ring / Q000008:administration & dosage*; D006801:Humans; D014411:Neoplastic Stem Cells / Q000187:drug effects; D038501:Tankyrases / Q000037:antagonists & inhibitors / Q000235:genetics*; D060449:Wnt Signaling Pathway / Q000187:drug effects; D051176:beta Catenin / Q000096:biosynthesis / Q000235:genetics
chemical_list: D060466:Axin Protein; D002945:Cisplatin; D005472:Fluorouracil; D006575:Heterocyclic Compounds, 3-Ring; D038501:Tankyrases; D051176:beta Catenin; C544261:XAV939; C418109:TNKS protein, human
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