Background: Puerarin is the major bioactive ingredient extracted from Pueraria lobata. Puerarin has an antitumor effect on many kinds of cancer. Accordingly, the aim of this study was to investigate the effect and mechanism of puerarin on thyroid cancer (TC) proliferation and apoptosis.

Methods: TC and normal thyroid cells experienced exposure to puerarin at 0, 10, 50, or 100 μg/mL. Impacts of short hairpin RNA of Kruppel-like factor 2 (shKLF2), KLF2 overexpression, and notch receptor 1 (NOTCH1) overexpression on the malignant biological phenotypes of TC cells were gauged by cell function experiments. Quantification of KLF2, NOTCH1, B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X (Bax), and Cleaved caspase 3 was completed using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analyses. KLF2 and NOTCH1 levels in TC were analyzed using the Encyclopedia of RNA Interactomes (ENCORI) project database. Through rescue experiments, whether the anti-tumor effect of puerarin on TC is realized via KLF2/NOTCH1 axis was dissected.

Results: Puerarin inhibited the malignant growth of TC cells by up-regulating KLF2, which was reversed by shKLF2. KLF2 was lowly expressed in TC. Notably, NOTCH1 was negatively regulated by KLF2 and was highly expressed in TC. NOTCH1 overexpression abrogated KLF2 overexpression-inhibited malignant growth of TC cells, which was manifested as increased cell proliferation and Bcl-2 as well as decreased cell apoptosis, Bax and Cleaved caspase 3.

Conclusion: Puerarin suppresses TC cell proliferation and apoptosis via the KLF2/NOTCH1 axis.