2. Academic Validation
  3. Sodium butyrate enhances sorafenib-induced ferroptosis and immunogenic cell death by modulating IRF2-Oasl2-cGAS pathway in colorectal cancer

Sodium butyrate enhances sorafenib-induced ferroptosis and immunogenic cell death by modulating IRF2-Oasl2-cGAS pathway in colorectal cancer

  • Mater Today Bio. 2025 Nov 1:35:102498. doi: 10.1016/j.mtbio.2025.102498.
Ying Xiang 1,  Jinyu Zheng 1,  Xinlu Zhao 1,  Lina Zhou 2,  Qiong Yan 1,  Yichun Ma 1,  Yue Zhou 3,  Ping Jiang 3,  Yi Fang 3,  Wenjun Li 3,  Yinya Pan 3,  Hongji Tao 3,  Wenying Li 1,  Fan Xiang 4,  Yang Hua 5,  Yuyi Li 6,  Chang Zheng 3,  Weihong Ge 2,  Yuhong Li 7,  Simin Yan 2,  Yun Zhu 1 2,  Guifang Xu 1 3 8 6
Affiliations

Affiliations

  • 1 Department of Gastroenterology, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, 210008, Jiangsu Province, China.
  • 2 Department of Pharmacy, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, 210008, Jiangsu Province, China.
  • 3 Department of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008, Jiangsu Province, China.
  • 4 Department of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, 212013, Jiangsu Province, China.
  • 5 Biotechnology, Advance Academic Programs, Zanvyl Krieger School of Arts and Sciences, Johns Hopkins University, Baltimore, MD, USA.
  • 6 Department of Gastroenterology, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.
  • 7 Cancer Research Laboratory, Chengde Medical College, Chengde, Hebei Province, China.
  • 8 Department of Gastroenterology, Taikang Xianlin Drum Tower Hospital, Nanjing, 21008, Jiangsu Province, China.
PMID: 41281652 DOI: 10.1016/j.mtbio.2025.102498
Abstract

While much attention has been focused on the direct cytotoxic effects of Anticancer agents on tumor cells, emerging evidence suggests that the induction of immunogenic cell death (ICD) and the consequent remodeling of the tumor microenvironment may critically influence overall therapeutic efficacy. Sorafenib, a multitargeted tyrosine kinase inhibitor, can induce Ferroptosis and thereby trigger ICD, offering the potential to overcome chemoresistance and coordinate systemic antitumor immunity. However, its therapeutic efficacy in colorectal Cancer (CRC) remains limited, attributing to its low efficiency in inducing ICD. Herein, this study investigates combined sodium butyrate (NaB) and sorafenib in liposomal co-delivery system (LipNaB@Sor) at an optimal 1:1 M ratio in CRC. LipNaB@Sor synergistically amplifies sorafenib-induced Ferroptosis and consequent ICD, concurrently activating antitumor immunity through dendritic cell maturation and cytotoxic CD8+ T cell recruitment. Mechanistically, IRF2-mediated Oasl2 downregulation activates the cGAS-STING pathway, augmenting DNA damage signaling cascades. In vivo validation demonstrates significant tumor suppression and prolonged survival without observable toxicity, establishing LipNaB@Sor as a translatable strategy to overcome therapy resistance in immunologically unresponsive CRC.

Keywords

Colorectal cancer; Immunogenic cell death; Liposome; Sodium butyrate; Sorafenib.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z