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Curcumin inhibits the invasion and migration of pancreatic cancer cells by upregulating TFPI-2 to regulate ERK- and JNK-mediated epithelial–mesenchymal transition

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Abstract

Purpose

Pancreatic cancer (PC) is one of the most deadly human malignancies. Curcumin is a natural polyphenolic compound with wide-ranging pharmacological effects. Growing evidence suggests that curcumin has anticancer activity against PC, but the mechanism remains incompletely elucidated. This study aimed to investigate the effects and mechanisms of curcumin on the invasion and migration of PC cells.

Methods

Effect of curcumin on tissue factor pathway inhibitor (TFPI)-2 mRNA expression in PC cells was initially identified using qRT-PCR. Cytotoxicity of curcumin was assessed with MTT assays and IC50 was calculated. Involvement of ERK and JNK pathways, as well as protein expression of TFPI-2 and epithelial–mesenchymal transition (EMT)-related markers, were detected using immunoblotting. Invasion and migration of PC cells were examined using Transwell assays. TFPI-2 expression was manipulated by transfection with siRNA and shRNA. Rescue assays were used to validate the effect of curcumin on cell invasion and migration via TFPI-2.

Results

Curcumin increased the expression of TFPI-2 mRNA and protein in PC cells and attenuated cell invasion and migration. Curcumin also inhibited ERK and JNK pathways and EMT in PC cells. Knockdown of TFPI-2 partially reversed the inhibition of ERK and JNK pathways and EMT by curcumin. Mechanistically, curcumin upregulated TFPI-2, thereby inhibiting the ERK and JNK pathways, leading to the inhibition of EMT in PC cells.

Conclusion

Collectively, curcumin inhibits ERK- and JNK-mediated EMT through upregulating TFPI-2, which in turn suppresses the migration and invasion of PC cells. These findings provide new insights into the antitumor mechanism of curcumin.

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Data availability

The data generated in this study are available from the corresponding author upon reasonable request.

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Funding

This work was supported by the Zhejiang Provincial Natural Science Foundation of China (grant no. LGF19H290004).

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  1. Lu-Lu Zhai and Wei-Bo Li contributed equally to this work.

Authors and Affiliations

  1. Department of General Surgery, Division of Life Sciences and Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of China, 17 Lujiang Road, Hefei, 230001, People’s Republic of China

    Lu-Lu Zhai & Da-Long Yin

  2. Department of General Surgery, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, 261 Huansha Road, Hangzhou, 310006, People’s Republic of China

    Lu-Lu Zhai & Tong-Fa Ju

  3. Department of General Surgery, Renmin Hospital of Wuhan University, 99 Zhangzhidong Road, Wuhan, 430060, People’s Republic of China

    Lu-Lu Zhai, Wei-Bo Li, Long-Jiang Chen & Wei Wang

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Contributions

LLZ, TFJ, and DLY contributed to conception and design of the study. LLZ, WBL, LJC, and WW performed the experimental work. LLZ, WBL, LJC, and TFJ performed the statistical analysis. LLZ, WBL, LJC, WW, and TFJ wrote the draft of the manuscript. All authors contributed to manuscript revision, read, and approved the submitted version.

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Correspondence to Tong-Fa Ju or Da-Long Yin.

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Zhai, LL., Li, WB., Chen, LJ. et al. Curcumin inhibits the invasion and migration of pancreatic cancer cells by upregulating TFPI-2 to regulate ERK- and JNK-mediated epithelial–mesenchymal transition. Eur J Nutr 63, 639–651 (2024). https://doi.org/10.1007/s00394-023-03296-5

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