Atractylenolide I inhibits the growth, proliferation and migration of B16 melanoma cells via the PI3K/AKT/mTOR pathway

Xu,Xiaochun; Kang,Ping; Che,Hong

doi:10.3892/ol.2025.15118

Atractylenolide I inhibits the growth, proliferation and migration of B16 melanoma cells via the PI3K/AKT/mTOR pathway

Authors:
- Xiaochun Xu
- Ping Kang
- Hong Che
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Affiliations: Department of Dermatology, Ordos Central Hospital, Ordos, Inner Mongolia Autonomous Region 017010, P.R. China
Published online on: May 30, 2025 https://doi.org/10.3892/ol.2025.15118
Article Number: 372
Copyright: © Xu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Melanoma is a malignancy that affects millions of individuals worldwide. Atractylenolide I (AT) has been reported to suppress cell proliferation in melanoma cells, but the underlying mechanism is not fully understood. Therefore, the present study investigated the mechanism underlying the antitumor activity of AT in melanoma. Cell Counting Kit‑8 and colony formation assays were performed after B16 and A875 melanoma cells were treated with 25, 50 and 100 µM AT. The results indicated that AT could significantly and dose‑dependently suppress melanoma cell viability and proliferation (P<0.001). Furthermore, the stemness and migration of melanoma cells were significantly inhibited by the three doses of AT (P<0.001), as demonstrated by sphere formation and wound healing assays. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes and target‑pathway networks analyses identified the phosphatidylinositol 3‑kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) axis as a potential target of AT in melanoma. Mechanistically, the suppression of viability, proliferation, stemness and migration by AT was significantly reversed by overexpression of PI3K in melanoma cells. However, AT did not affect melanoma cells when PI3K was knocked down, suggesting that the anti‑melanoma effects of AT are mediated by PI3K. Additionally, the expression of phosphorylated (p‑)PI3K, PI3K, p‑AKT (Ser⁴⁷³), p‑AKT (Thr³⁰⁸), AKT, p‑mTOR (Ser²⁴⁴⁸), p‑mTOR (Ser²⁴⁸¹) and mTOR, determined via western blotting, revealed that the phosphorylation of PI3K, AKT and mTOR was significantly suppressed following AT treatment (P<0.001), further supporting the notion that AT exerts its antitumor activity through the PI3K/AKT/mTOR axis. In conclusion, the present study demonstrated that AT could inhibit the viability, proliferation and migration of melanoma cells through the PI3K/AKT/mTOR axis. These findings reveal a novel anti‑melanoma effect and the therapeutic potential of AT in melanoma.

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