Year: 2016
Type: article
Abstract: T24-RGEM/UMUC3-RGEM, were newly established at our laboratory.Cell lines were treated with 1mM 5-Aza-CdR for 24 hours on day 1, with CDDP (5mg/ml) and GEM (30nmol/ml) on day 2, or combinatorial treatment of 5-Aza-CdR (day 1) and either CDDP or GEM (day 2).The cell phonotypical alterations were monitored by cell double time, DNA methylation changes and gene expression changes.RESULTS: We used the Illumina Infinium Human Methyl-ation450 BeadArray to measure the DNA methylation changes at 482,421 CpGs, and found dramatic DNA methylation alterations between T24 and UMUC3 bladder cancer cell lines, as well as their drugresistance counterparts (T24-RCDDP/T24-RGEM and UMUC3-RCDDP/UMUC3-RGEM).We identified DNA hypermethylation at 28,271 and 45,927 CpG sites in T24 and UMUC3 drug resistant cells, respectively.Furthermore, we identified DNA hypomethylation at 41,576 and 18,711 CpG sites in T24 and UMUC3 drug resistant cells, respectively.In addition, 5-Aza-CdR may re-sensitize CDDP-resistant cell lines, since the cell double time significantly increased from 70 (T24-RCDDP) or 86 (UMUC3-RCDDP) hours by CDDP alone to 495 (T24-RCDDP) or 721(UMUC3-RCDDP) hours after the combination treatments.However, it should be noted that the combination treatment of 5-Aza-CdR with GEM did not re-sensitize the chemotherapeutic effect on GEM-resistant cells.CONCLUSIONS: Overall, our results indicate that alteration of DNA methylation may play an important role in drug-resistance, while DNA methylation re-programming may also sensitize the chemotherapeutic efficacy for drug resistance cells especially in metastatic urothelial carcinoma.
Source: The Journal of Urology
Authors: Alexander Sankin, Benjamin Gartrell, Kerwin Cumberbatch, Hongying Huang, Mark Schoenberg, Xingxing Zang
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W2317002240