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Tropical Journal of Pharmaceutical Research
Pharmacotherapy Group, Faculty of Pharmacy, University of Benin, Benin City, Nigeria
ISSN: 1596-5996 EISSN: 1596-5996
Vol. 16, No. 4, 2017, pp. 803-810
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Bioline Code: pr17102
Full paper language: English
Document type: Research Article
Document available free of charge
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Tropical Journal of Pharmaceutical Research, Vol. 16, No. 4, 2017, pp. 803-810
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Septin 9 hypermethylation contributes to migration and resistance to drug treatments in colon cancer
Peng, Tao; Kong, Fanguo; Diao, Xingyuan; Huang, Jiaguo & Liu, Xishuang
Abstract
Purpose: To examine septin 9 gene-promoter methylation content in colorectal cancer and establish its
significance in cancer progression and chemoresistance.
Methods: Patient samples and colorectal cancer cell lines (CRC) were evaluated for septin 9
expression and promoter hypermethylation content. Septin 9 promoter methylation and expression in
cells were perturbed by 5-AZA (5-aza-2'-deoxycytidine) treatments or overexpression and probed for
changes in Rho A signaling, cell proliferation, and migration. Finally, the significance of septin 9
methylation in chemoresistance was probed using apoptotic assays in CRC cells and in a xenograft
tumor model.
Results: Expression analysis showed a reduction in septin 9 levels in tumor tissues (p < 0.001) and cell
lines (p < 0.01), while an increase in septin 9 promoter methylation was seen, respectively ( > 2-fold; p <
0.01). Increasing septin 9 levels in CRC cells by 5-AZA treatments or overexpression showed
decreased Rho A signaling and cell migration (p < 0.01), whereas cell proliferation remained unaffected.
Furthermore, increasing septin 9 levels also exhibited increased cisplatin-induced apoptosis in CRC
cells and reduced chemoresistance in the mouse (~2-fold; p < 0. 01).
Conclusion: Septin 9 promoter hypermethylation reduces septin 9 expression and promotes migration
and chemoresistance.
Keywords
Septin 9, Hypermethylation, Colorectal cancer, Drug resistance, Rho A signaling
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