Parthenolide increases the sensitivity of gastric cancer cells to chemotherapy. - GreenMedInfo Summary
Parthenolide increases the sensitivity of gastric cancer cells to chemotherapy.
J Tradit Chin Med. 2020 12 ;40(6):908-916. PMID: 33258341
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.