CDDO, a PPAR‑γ ligand, inhibits TPA‑induced cell migration and invasion through a PPAR‑γ‑independent mechanism

Jang,Hye-Yeon; Hong,On-Yu; Youn,Hyun Jo; Jung,Jaeuk; Chung,Eun Yong; Jung,Sung Hoo; Kim,Jong-Suk

doi:10.3892/ol.2022.13474

CDDO, a PPAR‑γ ligand, inhibits TPA‑induced cell migration and invasion through a PPAR‑γ‑independent mechanism

Authors:
- Hye-Yeon Jang
- On-Yu Hong
- Hyun Jo Youn
- Jaeuk Jung
- Eun Yong Chung
- Sung Hoo Jung
- Jong-Suk Kim
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Affiliations: Department of Biochemistry, Institute for Medical Sciences, Jeonbuk National University Medical School, Jeonju, Jeollabuk 54907, Republic of Korea, Department of Surgery, Research Institute of Clinical Medicine of Jeonbuk National University, Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju, Jeollabuk 54907, Republic of Korea, Department of Anesthesiology and Pain Medicine, Bucheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea
Published online on: August 22, 2022 https://doi.org/10.3892/ol.2022.13474
Article Number: 354
Copyright: © Jang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Peroxisome proliferator‑activated receptor‑γ (PPAR‑γ) acts as a key factor in breast cancer metastasis. Notably, PPAR‑γ can inhibit metalloproteinase (MMP), which is involved in cancer metastasis. Our previous study revealed that PPAR‑γ was related to breast cancer metastasis. The present study aimed to investigate whether the PPAR‑γ ligand 2‑cyano‑3,12‑dioxooleana‑1,9‑dien‑28‑oic acid (CDDO) mediated suppression of cell invasion and reduced the expression of MMP‑9 in breast cancer cells. The results indicated that CDDO reduced MMP‑9 expression, cell migration and invasion of breast cancer cells by inhibiting TPA‑induced phosphorylation of mitogen‑activated protein kinases, and downregulating the activities of activator protein‑1 and nuclear factor κB. Notably, knock‑out of PPAR‑γ by small interfering RNA in MCF‑7 cells revealed that TPA‑induced MMP‑9 expression occurred through a PPAR‑γ‑independent pathway. These data indicated that the downregulatory effect of CDDO on MMP‑9 expression was affected by a mechanism independent of PPAR‑γ. In conclusion, the findings of the present study suggested that CDDO may act as a key agent in the regulation of breast cancer metastasis, suggesting CDDO as a new targeted therapy for breast cancer.

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