Abstract
In this study, we aimed to explore the effects of curcumin on the progression of colorectal cancer and its underlying mechanisms involved. Cell proliferation, apoptosis and invasion were determined through CCK-8 assay, colony formation assay, EdU assay, flow cytometry, and transwell invasion assay, respectively. The protein expression of Bax, MMP2, USP4 and LAMP3 was measured using western blot. Pearson correlation coefficient was used to evaluate the relationship between USP4 and LAMP3. Co-IP was also conducted to determine the interaction between USP4 and LAMP3. Xenograft tumor model was established to explore the role of curcumin in colorectal cancer in vivo. IHC was utilized to measure the expression of Bax, MMP2, USP4 and LAMP3 in tumor tissues from mice. Curcumin significantly accelerated cell apoptosis, and inhibited cell proliferation and invasion in LoVo and HCT-116 cells. LAMP3 was augmented in colorectal cancer tissues and cells, and curcumin could reduce the expression of LAMP3. Curcumin decreased LAMP3 expression to exhibit the inhibition role in the progression of colorectal cancer. USP4 interacted with LAMP3, and positively regulated LAMP3 expression in colorectal cancer cells. LAMP3 overexpression could reverse the suppressive effects of USP4 knockdown on the development of colorectal cancer. Curcumin downregulated USP4 to impeded the progression of colorectal cancer via repressing LAMP3 expression. In addition, curcumin obviously restrained tumor growth in mice through downregulating USP4 and LAMP3 expression. These data indicated that curcumin exert the anti-tumor effects on the development of colorectal cancer through modulating the USP4/LAMP3 pathway.
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Data availability
The data sets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
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P.M. designed and supervised the study. H.W. and X.L. conducted the experiments and drafted the manuscript. F.L. and Y.L. collected and analyzed the data. B.L. and X.H. contributed the methodology and prepared the figures. H.C. and B.W. operated the software and edited the manuscript. All authors reviewed the manuscript. The authors declare that all data were generated in-house and that no paper mill was used.
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All experiments were approved by the Research Ethics Committee of Nanyang First People’s Hospital and was carried out according to the guidelines of Declaration of Helsinki. Xenograft tumor experiments were ratified by the Ethical Committee of Nanyang First People’s Hospital and performed in accordance with the guidelines of the National Animal Care and Ethics Institution.
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Wei, H., Li, X., Liu, F. et al. Curcumin inhibits the development of colorectal cancer via regulating the USP4/LAMP3 pathway. Naunyn-Schmiedeberg's Arch Pharmacol 397, 1749–1762 (2024). https://doi.org/10.1007/s00210-023-02721-0
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DOI: https://doi.org/10.1007/s00210-023-02721-0