To investigate the influence of honokiol on cisplatin resistance in gastric cancer cells by regulating the nuclear transcription-related factor 2 (Nrf2) /antioxidant response element (ARE) pathway.

Human drug-resistant gastric cancer cell line SGC7901/DDP was cultured in vitro and treated with 5, 15 μg/mL honokiol, and 15 μg/mL honokiol + 1 mmol/L Nrf2/ARE pathway activator dimethyl fumarate (DMF) ; MTT assay was applied to detect cell proliferation; scratch assay and Transwell chamber were used to detect cell migration and invasion respectively; flow cytometry was used to detect apoptosis; and Western blot was applied to detect the expression of cellular Nrf2, heme oxygenase 1 (HO-1) , P-glycoprotein (P-gp) , multidrug resistance-related protein 1 (MRP1) , proliferating cell nuclear antigen (PCNA) , matrix metalloproteinase 2 (MMP2) , matrix metalloproteinase 9 (MMP9) , and cysteine protease 3 (caspase-3) and cleaved caspase-3; the SGC7901/DDP transplanted tumor nude mouse model has been established, and then randomly divide them into a control group, low-dose honokiol group, high-dose honokiol group, and Nrf2/ARE pathway activator group. The tumor volume and weight were detected after grouping processing. One-way ANOVA and Tukey tests were used to compare differences between groups.

Compared with the control group, the OD₄₉₀ value, scratch healing rate [ (31.24 ± 2.23) %, (25.36 ± 2.06) % vs (48.01 ± 2.13) %], invasion rate [ (38.61 ± 2.24) %, (29.57 ± 2.41) % vs (52.36 ± 2.13) %], tumor volume and mass, protein expressions of HO-1, P-gp, MRP1, PCNA, MMP2, MMP9 and nuclear Nrf2 were decreased in low and high-dose honokiol groups (all P < 0.05) , the apoptosis rate [ (27.24 ± 2.24) %, (38.56 ± 2.31) % vs (17.31 ± 3.12) %] and the protein expression of caspase-3 and cleaved caspase-3 were increased (all P < 0.05) ; compared with high-dose honokiol group, the OD₄₉₀ value, scratch healing rate [ (37.71 ± 2.17) % vs (25.36 ± 2.06) %], invasion rate [ (43.53 ± 2.37) % vs (29.57 ± 2.41) %], tumor volume and mass, protein expressions of HO-1, P-gp, MRP1, PCNA, MMP2, MMP9 and nuclear Nrf2 in the Nrf2/HO-1 pathway activator group were increased (all P < 0.05) , the apoptosis rate [ (21.48 ± 2.16) % vs (38.56 ± 2.31) %] and the protein expression of caspase-3 and cleaved caspase-3 were decreased (all P < 0.05) .

Honokiol may affect the cisplatin chemosensitivity of drug-resistant gastric cancer cell line SGC7901/DDP by regulating the Nrf2/ARE signaling pathway.