ANXA1/FPR Signaling Contribute to Paclitaxel Resistance in Ovarian Cancer Through PI3K/AKT-Associated PGC1α Regulation.

BACKGROUND

Ovarian cancer has the highest mortality among gynecologic malignancies, and acquired resistance to paclitaxel severely limits its clinical efficacy.

AIMS: This study aimed to investigate whether the ANXA1/FPR axis contributes to paclitaxel resistance in ovarian cancer and to elucidate the underlying molecular mechanisms.

METHODS AND

RESULTS

Using the ANXA1 mimetic peptide Ac2-26 and the FPR antagonist Boc2, we provided pharmacological evidence that activation of the ANXA1/FPR axis promotes paclitaxel resistance in ovarian cancer cells. Mechanistically, ANXA1/FPR signaling activated the PI3K/AKT pathway and upregulated PGC1α, leading to enhanced mitochondrial biogenesis and adaptive energy metabolism remodeling, which in turn prevented paclitaxel-induced cell death.

CONCLUSION

Our findings suggest that the ANXA1/FPR/PI3K/AKT/PGC1α axis may represent a potential therapeutic target for overcoming paclitaxel resistance in ovarian cancer.