As a novel proteasome inhibitor, remarkable proliferation inhibitory effect of compound YSY-01A was shown on tumor cells in previous studies. However, few studies has reported its effect on gastric cancer and related ...As a novel proteasome inhibitor, remarkable proliferation inhibitory effect of compound YSY-01A was shown on 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 agent 5-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-c~ and IFN induced NF-KB nuclear translocation. At the same time, the compound YSY-01A could reduce the expression of IKK-~, IL-I~ and iNOS, while it significantly enhanced the expression of COX-2 in MGC-803 ceils. Taken together, compound YSY-01A had an impressive tumor inhibitory effect, and it worked in NF-KB-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.展开更多
基金Eleventh Five-Year Plan for National Science and Technology Major Project(Grant No.2009ZX0930-010)National Science Foundation of China(Grant No.81172915)a grant from Major New Drug Research and Development Platform of PekingUniversity(Grant No.2009ZX09301-010)
文摘As a novel proteasome inhibitor, remarkable proliferation inhibitory effect of compound YSY-01A was shown on 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 agent 5-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-c~ and IFN induced NF-KB nuclear translocation. At the same time, the compound YSY-01A could reduce the expression of IKK-~, IL-I~ and iNOS, while it significantly enhanced the expression of COX-2 in MGC-803 ceils. Taken together, compound YSY-01A had an impressive tumor inhibitory effect, and it worked in NF-KB-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.
