OncoTargets and Therapy (Feb 2020)

Transcriptomics Analysis of the Tumor-Inhibitory Pathways of 6-Thioguanine in MCF-7 Cells via Silencing DNMT1 Activity

  • Li H,
  • An X,
  • Zhang D,
  • Li Q,
  • Zhang N,
  • Yu H,
  • Li Z

Journal volume & issue
Vol. Volume 13
pp. 1211 – 1223

Abstract

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Hao Li,1,* Xinglan An,1,* Daoyu Zhang,1 Qi Li,1 Nan Zhang,1 Hao Yu,2 Ziyi Li1 1Key Laboratory of Organ Regeneration and Transplantation of Ministry of Education, First Hospital, Jilin University, Changchun 130021, People’s Republic of China; 2College of Animal Sciences, Jilin University, Changchun 130062, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ziyi LiKey Laboratory of Organ Regeneration and Transplantation of Ministry of Education, First Hospital, Jilin University, Changchun 130021, People’s Republic of ChinaTel +86-431-8783-6187Email [email protected] YuCollege of Animal Sciences, Jilin University, Changchun 130062, People’s Republic of ChinaTel +86-159-4306-5187Email [email protected]: 6-thioguanine (6-TG), as a conventional “ancient” drug for the treatment of acute leukemia, has been proved to have extensive anti-tumor roles. This study was created to investigate the hidden function of 6-TG on the MCF-7 breast cancer cell line (ER+, PR+) and its mechanisms.Methods: MCF-7 cells were treated with 6-TG, and the IC50 value was measured by a cell counting kit-8 assay. Differentially expressed genes (DEGs) were confirmed by RNA-seq analysis. Apoptosis and cell cycle consequences were determined by flow cytometry and Western blot analyses.Results: The results showed that colony formation decreased markedly and the percentage of cell apoptosis increased after 6-TG treatment. DNMT1 mRNA and protein expression decreased, and FAS expression increased. Moreover, 6-TG also induced MCF-7 cells to undergo G2/M phase cell cycle arrest and upregulated CDKN1A (p21).Conclusion: Overall, our results suggest that 6-TG may induce FAS-mediated exogenous apoptosis and p21-dependent G2/M arrest by inhibiting the activity of DNMT1 in MCF-7 breast cancer cells.Keywords: 6-TG, MCF-7 breast cancer cells, apoptosis, cell cycle, DNMT1

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