Parthenolide inhibits the proliferation and migration of cervical cancer cells via FAK/GSK3ß pathway.

ABSTRACT

PURPOSE: Cervical cancer (CC) ranks as the fourth most prevalent malignancy among women worldwide, necessitating effective therapeutic interventions to mitigate its detrimental impact on both physical and mental health. Parthenolide (PTL), a natural product of the sesquiterpene lactone derived from Feverfew leaves, has exhibited promising anti-tumor properties in previous studies; however, its precise effects and underlying molecular mechanisms in CC remain elusive. METHODS: In this work, we investigated the effect of PTL on the proliferation and migration of CC cells. Western blot analysis and Reverse transcription­quantitative PCR were used for mechanistic elucidation. RESULTS: Our findings indicated that PTL substantially inhibited the proliferation of HeLa and SiHa CC cell lines in a dose- and time-dependent manner. Moreover, PTL significantly suppressed the migration of CC cells by down-regulating the expression of vascular endothelial growth factor (VEGF), metastasis-associated protein 1 (MTA1), and transforming growth factor-ß1 (TGF-ß1). Mechanistically, PTL blocked the phosphorylation of focal adhesion kinase (FAK) and glycogen synthase kinase-3ß (GSK3ß) induced by epidermal growth factor (EGF). Further investigations revealed that PTL suppressed the proliferation of CC cells by inhibiting the EGF-mediated phosphorylation of the FAK/GSK3ß signaling pathway. CONCLUSION: Taken together, the present in vitro results suggest that PTL may inhibit the proliferation and migration of CC cells through down-regulating the FAK/GSK3ß signaling pathway, providing new insights for the application of PTL in the treatment of CC.