Axin通过激活p53的表达抑制结肠癌细胞的生长

doi:10.3969/j.issn.1004-616x.2014.05.002

Abstract

Abstract:

OBJECTIVE: To investigate the effect of Axin on the biological behavior of SW480 colon cancer cells and to elucidate its molecular mechanism. METHODS：SW480 colon cancer cells were transfered with pCMV5-HA-Axin and pCMV5-HA and blank control group was desigined. Cell proliferation was detected by MTT assay and colony formation assay，and the cell cycle was analyzed by flow-cytometry. At the same time，Real-time PCR and Western blot were used to assess the expressions of Axin and p53 oncogene in SW480 cells. RESULTS：Over-expression of Axin significantly inhibited the growth of SW480 colon cancer cells. MTT assay revealed over-expression of Axin inhibited the proliferation of SW480 cells(P<0.05). Transfection of Axin increased colon cancer SW480 cell cycle pre G1 ratio，inhibited G1 phase and decreased S ratio(P<0.05). p53 mRNA doubled in SW480 cells with transfered pCMV5-HA-Axin(P<0.05). P53 protein was also doubled in SW480 cells with transfered pCMV5-HA-Axin compared with empty vector groups(P<0.05). CONCLUSION：Over-expression of Axin could significantly inhibit the growth of colon cancer cells，and its mechanism might be related to the activation of the p53 oncogene.

Key words: colon cancer, Axin, p53, proliferation, cell cycle

LU Jian-rong，DING Cai-xia，YUAN Yong，ZHANG Juan，CAI Lin. Axin inhibited the growth of colon cancer cells by activating p53[J]. Carcinogenesis, Teratogenesis & Mutagenesis, doi: 10.3969/j.issn.1004-616x.2014.05.002.

References

[1] 项芳芳，毛高平. 大肠癌与抑癌基因相关性的研究现状[J]. 世界华人消化杂志，2012，20(5)：394-398.

[2] Waaler Jo，Ondrej M，Lucie T，et al. A novel tankyrase inhibitor decreases canonical Wnt signaling in colon carcinoma cells and reduces tumor growth in conditional APC mutant mice[J]. Cancer Res，2012，72(11)：2822-2832.

[3] Segditsas S，Tomlinson I. Colorectal cancer and genetic alterations in the Wnt pathway[J]. Oncogene，2006，25(57)： 7531-7537.

[4] Dent P. Multi-kinse modulation for colon cancer therapy[J]. Biol Ther，2013，14(10)：877-878.

[5] Zeng L，Fagotto F，Zhang T，et al. The mouse fused locus encodes Axin，an inhibitor of the Wnt signaling pathway that regulates embryonic axis formation[J]. Cell，1997，90(1)： 181-192.

[6] Salahshor S，Woodgett A. The links between axin and carcinogenesis [J]. J Clin Pathol，2005，58(3)：225-236.

[7] Jin LH，Shao QJ，Luo W，et al. Detection of point mutations of the Axin1 gene in colorectal cancers[J]. Int J Cancer，2003， 107(5)：696-699.

[8] Dajani R，Fraser E，Roe SM，et al. Structural basis for recruitment of glycogen synthase kinase 3 beta to the axin-APC scaffold complex[J]. EMBO J，2003，22(3)：494-501.

[9] Behrens J，Lustig B. The Wnt connection to tumorigenesis[J]. Int J Dev Biol，2004，48(5/6)：477-487.

[10] Julius MA，Schelbert B，Hsu W，et al. Domains of axin and disheveled required for interaction and function in Wnt signaling [J]. Biochem Biophys Res Commun，2000，276(3)：1162-1169.

[11] Gao ZH，Seeling JM，Hill V，et al. Casein kinase I phosphorylates and destabilizes the beta-catenin degradation complex[J]. Proc Natl Acad Sci，2002，99(3)：1182-1187.

[12] Cong F，Varmus H. Nuclear-cytoplasmic shuttling of Axin regulates subcellular localization of beta-catenin[J]. Proc Natl Acad Sci，2004，101(9)：2882-2887.

[13] Li Q，Wang X，Wu X，et al. Daxx cooperates with the Axin/ HIPK2/p53 complex to induce cell death[J]. Cancer Res， 2007，67(1)：66-74.

[14] Rui Y，Xu Z，Lin S，et al. Axin stimulates p53 functions by activation of HIPK2 kinase through multimeric complex formation[J]. EMBO J，2004，23(23)：4583-4594.

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Axin inhibited the growth of colon cancer cells by activating p53

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