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Project

A potential role of aberrant DNA methylation in the chemoresistance in bladder cancer cells

Funder: Japan Society for the Promotion of Science

Funding period
JPY 4.5 M
USD 41 K
Funding amount
Abstract
We found that the treatment with 5-Aza-CdR strikingly suppressed tumor formation by CDDP-resistant BCa cells in nude mice . Because 5-Aza-CdR alone was sufficient to completely block the xenograft formation, no synergistic effect of 5-Aza-CdR plus CDDP was observed.miR-200b was associated with CDDP sensitivity in BCa cells, and its downregulation was associated with CpG island hypermethylation. Pharmacological demethylation using 5-aza-2'-deoxycytidine restored miR-200b expression, and the combination of 5-aza-2'-deoxycytidine + CDDP strongly inhibited T24RC cell proliferation. Microarray analysis revealed that miR-200b + CDDP induced genes involved in CDDP sensitivity or cytotoxicity, including IGFBP3, ICAM1 and TNFSF10, in the resistant cells. Expression and DNA methylation of miR-200b were inversely associated in primary BCa, and low expression/high methylation was associated with poor overall survival. T
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System

Categories
  • FOR (ANZSRC)

    1112 Oncology and Carcinogenesis

  • RCDC

    Cancer

  • RCDC

    Genetics

  • RCDC

    Prevention

  • HRCS HC

    Cancer

  • HRCS RAC

    2.1 Biological and endogenous factors

  • Health Research Areas

    Biomedical

  • Broad Research Areas

    Basic Science