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<p>Sunitinib, a multi-targeted receptor tyrosine kinase inhibitor with specificity for VEGFR, KIT, FLT3, and PDGFR, has demonstrated clinical efficacy as a first- to third-line treatment for refractory renal carcinoma. Our previous research indicated that sunitinib malate suppresses intestinal polyp proliferation by downregulating IL-6 mRNA expression, suggesting a potential analogous mechanism in colorectal carcinoma inhibition. This study aimed to elucidate the pharmacological effects and molecular mechanisms of sunitinib malate on colorectal carcinoma using HCT116, RKO, HT29, and SW480 cell lines in vitro and HCT116-derived xenografts in nude mice in vivo. We employed a comprehensive array of experimental techniques, including CCK-8/MTT assays for cell viability, Transwell and/or wound healing assays for migration, and Western blot and immunohistochemistry for protein expression analysis. Our findings demonstrate that sunitinib malate significantly inhibits colorectal cancer cell proliferation and migration in vitro. Moreover, in the xenograft model, sunitinib malate markedly suppressed colorectal tumor growth in vivo. Notably, we observed significant downregulation of c-MYC, TWIST, and MMP2 expression both in vitro and in vivo following sunitinib malate treatment. These results collectively suggest that sunitinib malate exerts its anti-colorectal carcinoma effects, at least in part, by disrupting the autocrine IL-6/STAT3/c-MYC/TWIST/MMP2 signaling axis.</p>

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Inhibition of colorectal carcinogenesis by sunitinib malate: disruption of the IL-6/STAT3/c-MYC/TWIST/MMP2 autocrine signaling axis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年5月23日

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  • Ling Qian,
  • Yi Yang,
  • Bin Zhao,
  • Pan Xu,
  • Ziyan Hu,
  • Liangwang Zhong,
  • Qi Dai,
  • Youbao Zhong,
  • Chao Yang,
  • Qinglong Shu,
  • Ray P. S. Han,
  • Yang Guan,
  • Zhiming Li,
  • Lai Chen

摘要

Sunitinib, a multi-targeted receptor tyrosine kinase inhibitor with specificity for VEGFR, KIT, FLT3, and PDGFR, has demonstrated clinical efficacy as a first- to third-line treatment for refractory renal carcinoma. Our previous research indicated that sunitinib malate suppresses intestinal polyp proliferation by downregulating IL-6 mRNA expression, suggesting a potential analogous mechanism in colorectal carcinoma inhibition. This study aimed to elucidate the pharmacological effects and molecular mechanisms of sunitinib malate on colorectal carcinoma using HCT116, RKO, HT29, and SW480 cell lines in vitro and HCT116-derived xenografts in nude mice in vivo. We employed a comprehensive array of experimental techniques, including CCK-8/MTT assays for cell viability, Transwell and/or wound healing assays for migration, and Western blot and immunohistochemistry for protein expression analysis. Our findings demonstrate that sunitinib malate significantly inhibits colorectal cancer cell proliferation and migration in vitro. Moreover, in the xenograft model, sunitinib malate markedly suppressed colorectal tumor growth in vivo. Notably, we observed significant downregulation of c-MYC, TWIST, and MMP2 expression both in vitro and in vivo following sunitinib malate treatment. These results collectively suggest that sunitinib malate exerts its anti-colorectal carcinoma effects, at least in part, by disrupting the autocrine IL-6/STAT3/c-MYC/TWIST/MMP2 signaling axis.