Synergistic combination of YS-1 and adriamycin inhibits human renal cancer through ERK1/2 signaling pathway in vitro and in vivo

  • Authors:
    • Xiaowen Yu
    • Qingqing Yang
    • Sensen Lin
    • Shengtao Yuan
    • Li Sun
  • View Affiliations

  • Published online on: January 16, 2017     https://doi.org/10.3892/or.2017.5373
  • Pages: 1756-1764
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Abstract

Adriamycin (ADM) is a principal drug for the treatment of renal cell cancer (RCC). Due to its limited response and high renal and cardiac toxicity, synergistic effects of ADM in combination with other drugs have been widely researched. In this study, we found the combination between YS-1 and ADM, performed higher anticancer activity on 786-O human RCC cells in vitro and in vivo, than that reported on its anti-angiogenesis effect compared with monotherapy of ADM. Our data showed that when combined with ADM, YS-1 promoted the sensitivity of 786-O cells to ADM. The combination of YS-1 and ADM also inhibited cell proliferation, but without affecting cell apoptosis. We found that ADM monotherapy treatment notably upregulated the activity of extracellular signal-regulated kinase ERK1 and ERK2 (ERK1/2), but when combined with YS-1, the p-ERK1/2 level was reduced; then inhibited the Ras/Raf/MEK pathway. Additionally, the synergistic effects on cell cycle arrest inhibition were eliminated when ERK1/2 was silenced using siRNA. Our combination therapy of YS-1 with ADM showed the strongest antitumor effects in vivo (inhibition ratio: 5 mg/kg YS-1 combined with 1 mg/kg ADM, 68.19%) in comparison with individual effects (inhibition ratio: 5 mg/kg YS-1, 30.07%; 1 mg/kg ADM, 50.42%). Collectively, these findings indicated that YS-1 did not only enhance the ability of ADM to inhibit tumor proliferation, but also reduce the renal toxicity to protect the normal renal tissues.
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March-2017
Volume 37 Issue 3

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Yu X, Yang Q, Lin S, Yuan S and Sun L: Synergistic combination of YS-1 and adriamycin inhibits human renal cancer through ERK1/2 signaling pathway in vitro and in vivo. Oncol Rep 37: 1756-1764, 2017.
APA
Yu, X., Yang, Q., Lin, S., Yuan, S., & Sun, L. (2017). Synergistic combination of YS-1 and adriamycin inhibits human renal cancer through ERK1/2 signaling pathway in vitro and in vivo. Oncology Reports, 37, 1756-1764. https://doi.org/10.3892/or.2017.5373
MLA
Yu, X., Yang, Q., Lin, S., Yuan, S., Sun, L."Synergistic combination of YS-1 and adriamycin inhibits human renal cancer through ERK1/2 signaling pathway in vitro and in vivo". Oncology Reports 37.3 (2017): 1756-1764.
Chicago
Yu, X., Yang, Q., Lin, S., Yuan, S., Sun, L."Synergistic combination of YS-1 and adriamycin inhibits human renal cancer through ERK1/2 signaling pathway in vitro and in vivo". Oncology Reports 37, no. 3 (2017): 1756-1764. https://doi.org/10.3892/or.2017.5373