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  • Title: Reversing effect of NOTCH1 inhibitor LY3039478 on drug-resistance cells SGC7901/DDP of human gastric cancer and its mechanism.
    Author: Wang YL, Zhang Y, Huang XY, Zheng Y.
    Journal: Eur Rev Med Pharmacol Sci; 2018 Jul; 22(13):4121-4127. PubMed ID: 30024600.
    Abstract:
    OBJECTIVE: To investigate the reversing effects of NOTCH1 inhibitor LY3039478 on cancer of the stomach's drug-resistance cells SGC7901/DDP and its relevant mechanism. MATERIALS AND METHODS: Drug-resistance cells SGC7901/DDP of human gastric cancer before and after reversal via NOTCH1 inhibitor LY3039478 were used as objects of study. Changes in the expression of Hes protein in cells were detected via Western blotting; the inhibitory effect of drugs on cell multiplication was detected via cell counting kit-8 (CCK-8), and the Rhodamin123 (Rh123) efflux and P-glycoprotein (P-GP) expression level in cells were detected by flow cytometry. RESULTS: NOTCH1 inhibitor LY3039478 could inhibit the expression of Hes protein in SGC7901/DDP cells. Under the effect of 1 μmol/L and 2 μmol/L NOTCH1 inhibitor LY3039478, drug sensitivity of SGC7901/DDP cells to cisplatin was increased by 2.2 times and 2.86 times, respectively. The content of Rh123 in cells was increased by 1.41 times and 2.62 times, respectively, but the P-GP expression level was decreased by 67.5% and 45%, respectively. CONCLUSIONS: NOTCH1 inhibitor LY3039478 can inhibit or even reverse the multidrug resistance-associated protein in SGC7901/DDP cells. The mechanism of drug resistance may be related to the decrease of Rh123 efflux and P-GP expression level in cancer cells.
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