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<p>One of the leading causes of cancer deaths worldwide is ovarian tumor metastasis. It is very common for ovarian cancer (OC) cells to metastasize to the peritoneum. Free-floating OC cells can drift in the ascitic fluid (fluid that accumulates in the abdominal cavity due to cancer) and attach to the peritoneal lining of the abdominal cavity. In OC, peritoneal metastasis is strongly associated with poor prognosis. This study compared the effects of RLIP inhibition in various OC cell lines and in an orthotopic mouse model of ovarian metastasis to assess its anti-proliferative and anti-metastatic activity. Relative to the control treatment, RLIP inhibition and/or depletion decreased in vitro cell viability and minimized migratory and invasive capabilities of OC cells. The in vivo model was performed using HeyA8 OC cells expressing the luciferase gene that were implanted into the mice followed by the treatment of the mice with RLIP antisense (RAS, 4&#xa0;mg/kg, b.w.), RLIP antibody (Rab, 4&#xa0;mg/kg, b.w.) and a combination of RLIP antisense and RLIP antibody (RAS + Rab). Primary tumor weight and metastatic lesions were reduced in both RAS-treated and Rab-treated mice compared to control mice. Mice that received the RAS + Rab combination had almost no metastasis, and their tumor weight was much lower than that seen with either agent alone. Survival was also extended in NSG mice inoculated with HeyA8-luc OC cells when treated with RLIP-targeting agents. Overall, our findings indicate that RLIP antisense together with RLIP antibodies may be effective in controlling primary tumor growth and peritoneal metastasis, supporting the need for continued investigation.</p>

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RLIP depletion suppresses ovarian cancer growth and metastasis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月30日

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  • B. Madhu Krishna,
  • Pankaj Garg,
  • David Horne,
  • Prakash Kulkarni,
  • Ravi Salgia,
  • Sharad S. Singhal

摘要

One of the leading causes of cancer deaths worldwide is ovarian tumor metastasis. It is very common for ovarian cancer (OC) cells to metastasize to the peritoneum. Free-floating OC cells can drift in the ascitic fluid (fluid that accumulates in the abdominal cavity due to cancer) and attach to the peritoneal lining of the abdominal cavity. In OC, peritoneal metastasis is strongly associated with poor prognosis. This study compared the effects of RLIP inhibition in various OC cell lines and in an orthotopic mouse model of ovarian metastasis to assess its anti-proliferative and anti-metastatic activity. Relative to the control treatment, RLIP inhibition and/or depletion decreased in vitro cell viability and minimized migratory and invasive capabilities of OC cells. The in vivo model was performed using HeyA8 OC cells expressing the luciferase gene that were implanted into the mice followed by the treatment of the mice with RLIP antisense (RAS, 4 mg/kg, b.w.), RLIP antibody (Rab, 4 mg/kg, b.w.) and a combination of RLIP antisense and RLIP antibody (RAS + Rab). Primary tumor weight and metastatic lesions were reduced in both RAS-treated and Rab-treated mice compared to control mice. Mice that received the RAS + Rab combination had almost no metastasis, and their tumor weight was much lower than that seen with either agent alone. Survival was also extended in NSG mice inoculated with HeyA8-luc OC cells when treated with RLIP-targeting agents. Overall, our findings indicate that RLIP antisense together with RLIP antibodies may be effective in controlling primary tumor growth and peritoneal metastasis, supporting the need for continued investigation.