Abstract: OBJECTIVE: To investigate the effect of parthenolide(PTL), a sesquiterpene lactone medicinal compound, on the sensitivity of the gastric cancer cell line SGC7901 and the DPP-and ADR-resistant sublines SGC7901/DDP and SGC7901/ADR to cisplatin[diamminedichloroplatinum(Ⅱ), DDP] and adriamycin(ADR) in vitro.METHODS: SGC7901, SGC7901/DDP, and SGC7901/ADR were treated with various concentrations of PTL alone or in combination with DDP or ADR. The effects on cell proliferation, apoptosis, and expression/activity of several proliferation/apoptosis-related proteins [B-cell lymphoma-2(Bcl-2), cyclin D1,nuclear factor-kappa B(NF-κB), and Caspase-8] and drug transporters(P-glycoprotein and multidrug resistance protein-1) were measured using flow cytometry, Western blotting, and in vitro activity assays.RESULTS: Treatment of SGC7901 cells with PTL inhibited cell growth, increased apoptosis, and sensitized the cells to DPP. Mechanistically, PTL treatment resulted in downregulation of NF-κB activity and Bcl-2 expression, and upregulation of Caspase-8 activity. Similarly, PTL co-treatment of SGC7901/DDP and SGC7901/ADR overcame their resistance to DDP and ADR, respectively, with concomitant inhibition of NF-κB, Bcl-2, Cyclin D1, P-glycoprotein, and multidrug resistance protein-1 expression and/or activity.CONCLUSION: PTL treatment decreases drug resistance in SGC7901, SGC7901/DDP, and SGC7901/ADR cells, as reflected by induction of apoptosis, inhibition of proliferation, downregulation of pro-survival and drug resistance pathways, and upregulation of pro-apoptotic pathways. Our results suggest that co-treatment with PTL may thus complement existing therapies for gastric cancer.

Key words: Parthenolide, Cisplatin, Adriamycin, Gastric cancer, Chemotherapy, Sensitivity