Work

RLIP depletion suppresses ovarian cancer growth and metastasis

Year: 2026

Type: article

Abstract: 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. Key findings of this study with potential clinical relevance include: • RLIP is an attractive therapeutic target with the ability to suppress human OC at multiple stages of development. • Reducing RLIP levels significantly inhibits OC cell growth and enhances apoptosis compared with controls. • RLIP blockade/depletion may serve as a broad-spectrum therapeutic strategy that remains effective regardless of common pathway differences among OC subtypes. • This is the first evidence from integrated in vitro and in vivo studies demonstrating the strong therapeutic promise of RLIP-targeting agents for treating metastatic OC.

Source: Journal of Ovarian Research

DOI: 10.1186/s13048-026-01985-3

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

Institutions: City Of Hope National Medical Center, City of Hope, Beckman Research Institute, GLA University

Language: English

Topic: Ovarian cancer diagnosis and treatment

Subfield: Reproductive Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,290