Hypoxia-Induced VGF Promotes Cell Migration and Invasion in Prostate Cancer via the PI3K/Akt Axis

Background: Metastasis is a major cause of prostate Cancer (PCa)-related deaths in men. Recent studies have indicated that VGF nerve growth factor inducible (VGF) affects tumor invasion and metastasis. The present study investigated whether VGF is abnormally expressed in PCa and affects PCa progression and investigated the specific regulatory mechanisms by which VGF affects PCa invasion and metastasis.

Methods: The sh- hypoxia-inducible factor1 alpha (HIF-1α) plasmid was transfected into human cell lines 22Rv1 and C4-2 to create cell lines with stable low expression and overexpression of VGF. Quantitative PCR (qPCR) was performed to detect VGF mRNA. Western blot was performed to detect invasive migration-related proteins. Akt Activator SC79 (4 μg/mL) was added. After adding docetaxel (4 nM) to cells transfected with sh-NC and sh-VGF, the capacity of the cells to migrate invasively was assessed using the Transwell and scratch assays. Nude mice were injected with cells stably transfected with sh-NC or sh-VGF and the metastasis of the Cancer cells was detected by live imaging and HE staining after the injection of docetaxel (10 mg/kg).

Results: Abnormal levels of VGF in PCa tissue and plasma samples were detected, and VGF knockdown suppressed PCa metastasis. VGF was also shown to affect the invasion and metastasis of PCa cells via PI3K/Akt signaling. VGF knockdown limited PCa metastasis and the inhibitory impact was higher when paired with docetaxel (p < 0.001). After hypoxia induction, both the mRNA and protein levels of VGF and HIF-1α increased, which is associated with a poor prognosis for PCa.

Conclusion: By stimulating the PI3K/Akt pathway, VGF encourages the invasive metastasis of PCa. As a result, targeting VGF may be a potential treatment approach for metastatic PCa therapy.

PI3K/Akt; VGF; metastasis; prostate cancer.