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Updated: Jan 11, 2026

Establishment of Hepatocarcinoma in BALB/c-nu Mice and Investigation of the Therapeutic Effect of the Sanleng Jiashen Formula

Establishment of Hepatocarcinoma in BALB/c-nu Mice and Investigation of the Therapeutic Effect of the Sanleng Jiashen Formula

Published on: January 26, 2024

Linoleic Acid Potentiates Response to Chemotherapy in Biliary Tract Cancer Through RARγ Activation.

Yinye Yao^1,2,3, Chunjing Xu⁴, Yongfu Shao⁵

¹Postgraduate Training Base Alliance of, Wenzhou Medical University (Zhejiang Cancer Hospital), Hangzhou, Zhejiang, China.

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology

|November 13, 2025

Summary

Linoleic acid (LA) enhances chemotherapy for biliary tract cancer (BTC) by activating retinoic acid receptor gamma (RARγ). This dual approach boosts cancer cell death and strengthens the immune response against tumors.

Keywords:

apoptosis biliary tract cancer chemotherapy linoleic acid retinoic acid receptor gamma tumor microenvironment

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Area of Science:

Oncology
Metabolomics
Cancer Immunology

Background:

Biliary tract cancer (BTC) has a poor prognosis, with limited efficacy of standard gemcitabine plus cisplatin (Gem/Cis) chemotherapy due to resistance.
Metabolic alterations are implicated in cancer treatment response, but specific metabolic factors influencing BTC chemosensitivity are not well understood.

Purpose of the Study:

To identify metabolic determinants of chemotherapy response in BTC.
To investigate the potential of linoleic acid (LA) as a chemosensitizer in BTC treatment.

Main Methods:

Untargeted and targeted metabolomics to analyze plasma samples from BTC patients.
In vitro and in vivo experiments to assess the effects of LA supplementation on Gem/Cis chemotherapy.
Mechanistic studies involving retinoic acid receptor gamma (RARγ) inhibition (pharmacological and genetic).

Main Results:

Elevated plasma linoleic acid (LA) levels correlated with chemotherapy-responsive BTC.
LA supplementation enhanced Gem/Cis-induced cytotoxicity in BTC models.
LA activated RARγ, which was essential for its chemosensitizing effects.
The LA-RARγ axis promoted cancer cell apoptosis and modulated the immune microenvironment (reduced PD-L1, increased CD8+ T cell activation).

Conclusions:

Linoleic acid (LA) is a novel metabolic modulator that can overcome chemotherapy resistance in biliary tract cancer (BTC).
LA potentiates Gem/Cis chemotherapy by activating the RARγ pathway, leading to increased apoptosis and enhanced anti-tumor immunity.