Kaempferol restrains the proliferation and invasion of lung adenocarcinoma cells by modulating the IGF-1R/PI3K/AKT signaling pathway and partially reversing EMT suppression

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Abstract

Background Conditional reprogramming (CR) technology enables rapid and long-term expansion of primary cells while preserving their tumor-specific traits, differentiation potential, and viability. Using this approach, we established primary lung adenocarcinoma cells to explore the antitumor mechanisms of kaempferol, a natural flavonoid known to inhibit proliferation, metastasis, and epithelial–mesenchymal transition (EMT) in various cancers. Methods Short tandem repeat (STR) analysis and immunofluorescence were performed to authenticate primary lung adenocarcinoma cells derived from a patient. The effects of kaempferol on proliferation and invasion were evaluated in this cellular model. Mechanistic insights were further obtained by Western blot analysis of key proteins in the IGF-1R/PI3K/AKT pathway and epithelial-mesenchymal transition (EMT)-related markers. Results STR analysis and immunofluorescence confirmed that the primary human lung adenocarcinoma cells maintained genetic stability during in vitro culture. Kaempferol treatment significantly suppressed the viability, proliferation, and invasive capacity of these cells. At the molecular level, kaempferol reduced phosphorylation of IGF-1R, PI3K, and AKT, while upregulating E-cadherin and downregulating vimentin and α-SMA expression, collectively indicating partial reversal of epithelial-mesenchymal transition. Conclusions The CR technique enables the successful culture of primary lung cancer cells while preserving their fundamental genetic characteristics. Moreover, kaempferol suppresses the proliferation and metastasis of primary human lung adenocarcinoma cells, likely through inhibiting the IGF-1R/PI3K/AKT pathway and partially reversing EMT. These findings suggest that kaempferol may represent a potential therapeutic agent for the treatment of lung adenocarcinoma.

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