Effects of compound YSY-01A, a novel proteasome inhibitor, on MGC-803 cells and its related mechanism

doi:10.5246/jcps.2014.09.077

Abstract

Abstract:

As a novel proteasome inhibitor, remarkable proliferation inhibitory effect of compound YSY-01A was shownon tumor cells in previous studies. However, few studies has reported its effect on gastric cancer and related mechanism. We evaluated the anti-proliferative effect of compound YSY-01A using MGC-803 cells and its anti-tumor effect using xenograft nu-BALB/c mouse model. Cell proliferation inhibition was assessed by SRB assay. Related protein expression levels were determined by Western blot assay. We observed that the compound YSY-01A had a significant proliferation inhibitory effect on MGC-803 cells in vitro. Experiment in vivo showed that the compound YSY-01A had a remarkable growth inhibitory effect on MGC-803 cells xenograft tumor when it was used either alone or in combination with the conventional chemotherapeutic agent5-fluorouracil (5-FU). Furthermore, YSY-01A and 5-FU had a synergistic effect on xenograft tumor. Results of molecular experiment showed that the compound YSY-01A had a remarkable inhibitory effect on TNF-α and IFN induced NF-κB nuclear translocation. At the same time, the compound YSY-01A could reduce the expression of IKK-β, IL-1β and iNOS, while it significantly enhanced the expression of COX-2 in MGC-803 cells. Taken together, compound YSY-01A had an impressive tumor inhibitory effect, and it worked in NF-κB-related pathway, suggesting that the compound YSY-01A was an effective therapeutic drug for patients with gastric cancer. Higher tumor cell growth inhibition after the treatment in a combination with 5-FU indicated that combining YSY-01A with 5-FU might be more effective for displaying tumor cell growth inhibitory effects on gastric cancer cells.

Key words: Proteasome inhibitor, YSY-01A, MGC-803 cell line, NF-κB, Anti-tumor

CLC Number:

R962

Supporting:

Yixin Chen, Xia Yuan, Zemei Ge, Fuxiang Ran, Jun Wu, Runtao Li, Jingrong Cui . Effects of compound YSY-01A, a novel proteasome inhibitor, on MGC-803 cells and its related mechanism[J]. Journal of Chinese Pharmaceutical Sciences, 2014, 23(9): 601-609.

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