2. Academic Validation
  3. Aloperine exerts anti-tumor effect and activates the tumor cell-intrinsic STING pathway in gallbladder cancer

Aloperine exerts anti-tumor effect and activates the tumor cell-intrinsic STING pathway in gallbladder cancer

  • Int Immunopharmacol. 2025 Sep 23:166:115590. doi: 10.1016/j.intimp.2025.115590.
Yushun Chang 1,  Jie Lin 1,  Bo Yang 1,  Yuxuan Shen 1,  Weijun Zhao 1,  Hao Shen 1,  Quan Yang 1,  Haowen Lu 1,  Xiujun Cai 2,  Yifan Wang 3,  Wen Hua 4
Affiliations

Affiliations

  • 1 Department of General Surgery, Sir Run Run Shaw Hospital Affiliated to School of Medicine, Zhejiang University, Hangzhou 310016, China; National Engineering Research Center of Innovation and Application of Minimally Invasive Instruments, Hangzhou 310016, China; Zhejiang Provincial Key Laboratory of Laparoscopic Technology, Sir Run Run Shaw Hospital Affiliated to School of Medicine, Zhejiang University, Hangzhou 310016, China.
  • 2 Department of General Surgery, Sir Run Run Shaw Hospital Affiliated to School of Medicine, Zhejiang University, Hangzhou 310016, China; National Engineering Research Center of Innovation and Application of Minimally Invasive Instruments, Hangzhou 310016, China; Zhejiang Provincial Key Laboratory of Laparoscopic Technology, Sir Run Run Shaw Hospital Affiliated to School of Medicine, Zhejiang University, Hangzhou 310016, China. Electronic address: srrsh_cxj@zju.edu.cn.
  • 3 Department of General Surgery, Sir Run Run Shaw Hospital Affiliated to School of Medicine, Zhejiang University, Hangzhou 310016, China; National Engineering Research Center of Innovation and Application of Minimally Invasive Instruments, Hangzhou 310016, China; Zhejiang Provincial Key Laboratory of Laparoscopic Technology, Sir Run Run Shaw Hospital Affiliated to School of Medicine, Zhejiang University, Hangzhou 310016, China. Electronic address: anwyf@zju.edu.cn.
  • 4 Department of Respiratory Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, China. Electronic address: huawen@zju.edu.cn.
PMID: 40991999 DOI: 10.1016/j.intimp.2025.115590
Abstract

Background: Aloperine (ALO), a quinolizidine-type alkaloid isolated from a natural Chinese herb, exhibits Anticancer activity in several malignancies, but its efficacy and mechanisms in gallbladder Cancer (GBC) remain undefined.

Methods: Human GBC cell lines (GBCs) were treated with ALO and assessed for viability, colony formation, 5-Ethynyl-2'-deoxyuridine (EdU) incorporation and Apoptosis. Autophagic flux and related signaling were evaluated by western blotting and immunofluorescence. In vivo antitumor activity was determined in a nude mouse xenograft model.

Results: ALO markedly inhibited the proliferation ability of GBCs and disrupted autophagosome-lysosome fusion, leading to Reactive Oxygen Species (ROS) accumulation and Apoptosis. Furthermore, ALO induced DNA damage and nuclear release of double-stranded DNA (dsDNA) to cytoplasm, leading to cyclic-GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING)-mediated interferon (IFN) pathway activation and enhancing natural killer cells (NK cells) activation in vitro. In vivo, ALO reduced subcutaneous GBCs xenograft volume and weight and, along with increased cleaved Caspase-3 and Bax expression in tumor tissues, confirming tumor cell Apoptosis.

Conclusions: These findings indicate that ALO may serve as a novel therapeutic candidate for gallbladder Cancer by inhibiting autophagic flux to induce ROS-mediated Apoptosis while activating the cGAS-STING-IFN pathway to enhance antitumor immunity.

Keywords

Aloperine; Apoptosis; Autophagy; Gallbladder cancer; STING pathway.

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