Ginkgolic Acid Suppresses Nasopharyngeal Carcinoma Growth by Inducing Apoptosis and Inhibiting AKT/NF-κB Signaling

Area of Science:

• Oncology
• Pharmacology
• Natural Products

Background:

• Nasopharyngeal carcinoma (NPC) poses a significant health burden in endemic regions, with distant metastasis leading to poor prognoses.
• Novel anticancer strategies are crucial for managing NPC, especially given its metastatic potential.

Purpose of the Study:

• To investigate the antitumor effects of ginkgolic acid (GA) on nasopharyngeal carcinoma (NPC).
• To elucidate the underlying mechanisms of GA's action in NPC cells and its efficacy in vivo.
• To evaluate GA's potential as an adjuvant therapy in combination with 5-fluorouracil (5-FU).

Main Methods:

• Utilized NPC cell lines (5-8F, CNE2) and immortalized nasopharyngeal epithelial cells (NP69).
• Assessed GA's effects on cell survival, invasion, apoptosis, and cell cycle progression.
• Employed xenograft models to evaluate GA's efficacy in vivo.
• Analyzed key protein markers including Bcl2, Bax, PARP, caspases, and cell cycle regulators.

Main Results:

• GA significantly decreased NPC cell survival and invasion while inducing dose-dependent apoptosis.
• GA treatment led to G0/G1 phase arrest in NPC cells by downregulating CDK6, Cyclin D2, and Cyclin D3.
• GA inhibited the Akt/NF-κB signaling pathway.
• Combination therapy with GA and 5-FU enhanced 5-FU-induced apoptosis and potentiated GA's effects.

Conclusions:

• Ginkgolic acid demonstrates significant anticancer properties against nasopharyngeal carcinoma.
• GA induces NPC cell apoptosis and cell cycle arrest through specific molecular pathways.
• GA holds promise as an effective adjuvant therapy to conventional chemotherapy for NPC, potentially improving treatment outcomes.