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J Gastroenterol Hepatol. 2007 May;22(5):683-9.

Methylation of Ras association domain family protein 1, isoform A correlated with proliferation and drug resistance in hepatocellular carcinoma cell line SMMC-7721.

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Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, China.



It has been proposed that aberrant DNA methylation can alter cancer's response to therapeutic agents. The purpose of the present study was to investigate the relationship between Ras association domain family protein 1, isoform A (RASSF1A) and drug resistance or growth of hepatocellular carcinoma cell line SMMC-7721.


Methylation status of RASSF1A from genomic gene of SMMC-7721 was determined with methylation-specific polymerase chain reaction and was further verified by demethylation treatment with 5-aza-2'-deoxycytidine. Wild-type RASSF1A cDNA was introduced into SMMC-7721; chemosensitivity to cisplatin, mitomycin and fluorouracil were analyzed using 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide assay. Growth of cells was detected by colony formation assay and xenograft model.


RASSF1A was inactivated in SMMC-7721 cell line through epigenetic hypermethylation, and reintroduction of RASSF1A was markedly able to reduce the resistance to some anticancer drugs and inhibit the growth of cancer cells either in vitro or in vivo.


These results correlate methylation status of RASSF1A with biological profiles of SMMC-7721 and thus, associate methylation with cancer therapy. RASSF1A may be useful to predict treatment response and help to develop novel treatment strategies for clinical treatment of hepatocellular carcinoma.

[Indexed for MEDLINE]

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