Their results revealed that DNA hypermethylation may


Their results revealed that DNA hypermethylation may

contribute to the onset of the chemoresistance in ovarian cancer. In our study on cell lines, almost complete methylation pattern of the TGFBI promoter in 2 paclitaxel-resistant cell lines (SKOV3/TR and A2780/TR) was observed, with a complete loss or low level of TGFBI expression in these cell lines. In contrast, only sparsely methylated or unmethylated CpG sites were identified in cell lines with a rich level of TGFBI expression, including SKOV3, A2780, OVCAR8, and SKOV3/DDP ovarian cancer cell lines. Our results identified strong relation Salubrinal research buy between TGFBI expression and response to chemotherapy. To our knowledge, this is the first evidence of TGFBI hypermethylation as a mechanism of paclitaxel chemoresistance in ovarian cancer. Further, Veliparib our results were confirmed by using DNA methylation inhibitors. The relative expression of TGFBI mRNA and protein increased significantly after

treating with 5-aza-dc in palitaxel-resistant cells. However, no statistical differences of TGFBI expression were found after 5-aza-dc administration in other 4 cell lines. In addition, MTT assay showed that the rate of cell inhibition was significantly increased in SKOV3/TR and A2780/TR after 5-aza-dc treatment, which suggested that chemotherapy sensitivity to paclitaxel was enhanced and chemoresistance was reversed. In conclusion, Morin Hydrate our study indicated that promoter hypermethylation of TGFBI is a selleck frequent event in ovarian cancer. TGFBI methylation was associated with paclitaxel chemoresistance, and it can be used as a potential epigenetic biomarker and therapeutic target of paclitaxel resistance in ovarian cancer. Acknowledgements This work was supported by grants from National Natural Science Foundation of China (No. 81001167, No. 81172480/H1621, No. 81101973/H1621). References 1. Siegel R, Ward E, Brawley O, Jemal A: Cancer statistics, 2011: the impact of eliminating socioeconomic

and racial disparities on premature cancer deaths. CA Cancer J Clin 2011, 61:212–236.PubMedCrossRef 2. Matei D: Novel agents in ovarian cancer. Expert Opin Investig Drugs 2007, 16:1227–1239.PubMedCrossRef 3. McGuire WP, Hoskins WJ, Brady MF, et al.: Cyclophosphamide and cisplatin compared with paclitaxel and cisplatin in patients with stage III and stage IV ovarian cancer. N Engl J Med 1996, 334:1–6.PubMedCrossRef 4. Taniguchi T, Tischkowitz M, Ameziane N, et al.: Disruption of the Fanconi anemia-BRCA pathway in cisplatin-sensitive ovarian tumors. Nat Med 2003, 9:568–574.PubMedCrossRef 5. Ferrandina G, Zannoni GF, Martinelli E, et al.: Class III beta-tubulin overexpression is a marker of poor clinical outcome in advanced ovarian cancer patients. Clin Cancer Res 2006, 12:2774–2779.PubMedCrossRef 6. Yoshikawa H, Matsubara K, Qian GS, et al.

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