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Triptolide, a major component in the extract of Chinese herbal plant Tripterygium wilfordii Hook f (TWHf), has potential anti-neoplastic eect. In the present study we investigated the potential therapeutic eects and mechanisms of triptolide against human gastric cancer cells. Four gastric cancer cell lines with dierent p53 status, AGS and MKN-45 (wild type p53); MKN-28 and SGC-7901 (mutant p53) were observed as to cell growth inhibition and induction of apoptosis in response to triptolide treatment. We showed that triptolide inhibited cell growth, induced apoptosis and suppressed NK-kB and AP-1 transactivation in AGS cells with wild-type p53. Triptolide induced apoptosis by stimulating the expressions of p53, p21 waf1/cip1 , bax protein, and increased the activity of caspases. In addition, it caused cell cycle arrest in the G 0 /G 1 phase. To examine the role of p53 in these functions, we showed that suppression of p53 level with antisense oligonucleotide abrogated triptolide-induced apoptosis and over-expression of dominant negative p53 abolished the inhibitory eect on NF-kB activation. Furthermore, we demonstrated that triptolide had dierential eects on gastric cancer cells with dierent p53 status. We showed that triptolide also inhibited cell growth and induced apoptosis in MKN-45 with wild-type p53, whereas it had no signi®cant growthinhibition and apoptosis induction eects on the MKN-28 and SGC-7901 cells with mutant p53. Our data suggest that triptolide exhibits anti-tumor and anti-in¯ammatory eects by inhibiting cell proliferation, inducing apoptosis and inhibiting NF-kB and AP-1 transcriptional activity. However, a functional p53 is required for these proapoptotic, anti-in¯ammatory and anti-tumor eects. Oncogene (2001) 20, 8009 ± 8018.

Our findings suggest that EZH2 protein, as examined by immunohistochemistry, may serve as a promising diagnostic biomarker of HCCs, and the use of a three-marker panel (EZH2, HSP70 and GPC3) can improve the rate of detection of HCCs in liver biopsy tissues.

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