Journal of Chinese Pharmaceutical Sciences ›› 2014, Vol. 23 ›› Issue (9): 601-609.DOI: 10.5246/jcps.2014.09.077

• Original articles • Previous Articles     Next Articles

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

Yixin Chen1, Xia Yuan1, Zemei Ge2, Fuxiang Ran1, Jun Wu1, Runtao Li2*, Jingrong Cui1*    

  1. 1. State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, Beijing 100191, China
    2. Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China
  • Received:2014-05-15 Revised:2014-05-28 Online:2014-09-23 Published:2014-06-08
  • Contact: Tel.:86-10-82802467, 86-10-82801504
  • Supported by:
    Eleventh Five-Year Plan for National Science and Technology Major Project (Grant No. 2009ZX0930­010), National Science Foundation of China (Grant No. 81172915) and a grant from Major New Drug Research and Development Platform of Peking University (Grant No. 2009ZX09301­010).


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

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