2. Academic Validation
  3. A novel multifunctional mitochondrion-targeting NIR fluorophore probe inhibits tumour proliferation and metastasis through the PPARγ/ROS/β-catenin pathway

A novel multifunctional mitochondrion-targeting NIR fluorophore probe inhibits tumour proliferation and metastasis through the PPARγ/ROS/β-catenin pathway

  • Eur J Med Chem. 2023 Oct 5;258:115435. doi: 10.1016/j.ejmech.2023.115435.
Jianv Wang 1,  Jing Jia 2,  Qingqing He 1,  Yang Xu 1,  Hongye Liao 1,  Xia Xiong 1,  Li Liu 3,  Changzhen Sun 4
Affiliations

Affiliations

  • 1 Department of Dermatology, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China.
  • 2 Department of Anesthesiology, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China.
  • 3 Department of Dermatology, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China. Electronic address: liuli@swmu.edu.cn.
  • 4 Drug Research Center of Integrated Traditional Chinese and Western Medicine, National Traditional Chinese Medicine Clinical Research Base, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, 646000, China. Electronic address: sunchangzhen@swmu.edu.cn.
PMID: 37327679 DOI: 10.1016/j.ejmech.2023.115435
Abstract

Recent advancements in tumour-targeted therapies and immunotherapy offer hope to patients with various malignancies. However, the uncontrolled growth and metastatic infiltration of malignant tumours remain a huge therapeutic challenge. Therefore, this study aimed to develop an integrated multifunctional diagnostic and treatment reagent IR-251 that can not only be used for tumour imaging but also to inhibit tumour growth and metastasis. Besides, our results showed that IR-251 targeted and damaged the mitochondria in Cancer cells via organic anion-transporting polypeptides. Mechanistically, IR-251 induced ROS overproduction by inhibiting PPARγ and then inhibiting the β-catenin signalling pathway and downstream protein molecules related to the cell cycle and metastasis. Moreover, the excellent anti-tumour proliferation and metastasis ability of IR-251 were verified in vitro/in vivo. And Histochemistry staining revealed that IR-251 inhibited tumour proliferation and metastasis, which showed no significant side effect. In conclusion, this novel, multifunctional, mitochondria-targeting near-infrared fluorophore probe IR-251 has great potential in achieving accurate tumour imaging and inhibiting tumour proliferation and metastasis, and the underlying mechanism of action of IR-251 is mainly via the PPARγ/ROS/β-catenin pathway.

Keywords

Cancer therapy; Mitochondrion-targeted; Near-infrared imaging; Proliferation and metastasis; ROS.

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