Regulation and molecular mechanism of adiponectin on the proliferation, apoptosis, autophagy, and chemosensitivity of...

Area of Science:

• Oncology
• Molecular Biology
• Biochemistry

Background:

• Glioblastoma (GBM) remains a significant challenge in neuro-oncology.
• Adiponectin, a key adipokine, has shown potential anti-cancer effects in various studies.
• Understanding adiponectin's role in glioma cell lines is crucial for developing novel therapeutic strategies.

Purpose of the Study:

• To investigate the regulatory mechanisms of adiponectin on apoptosis and proliferation in the LN18 glioma cell line.
• To explore the impact of adiponectin on the chemosensitivity of LN18 cells to temozolomide (TMZ).
• To elucidate the involvement of AMPK and Akt signaling pathways in adiponectin's effects.

Main Methods:

• Cell proliferation was assessed using the cholecystokinin (CCK8) assay.
• Western blot analysis was used to evaluate protein expression (p-Akt, p-AMPK, p-mTOR, cleaved caspase3, Bax, Cyclin D1, Cyclin B1).
• Apoptosis and cell cycle were analyzed by AnnexinV/PI and PI staining flow cytometry, respectively. Autophagy markers (Beclin1, LC3II/I, p62) were also assessed.

Main Results:

• Adiponectin upregulated p-AMPK and downregulated p-mTOR, with no effect on p-Akt in LN18 cells.
• Adiponectin inhibited LN18 cell proliferation, increased apoptosis (elevated cleaved caspase3 and Bax), and induced G1 cell cycle arrest.
• Adiponectin promoted autophagy (increased Beclin1 and LC3II/I ratio, decreased p62) and enhanced TMZ's inhibitory effect on LN18 cell proliferation.

Conclusions:

• Adiponectin impedes proliferation, induces apoptosis and autophagy in the LN18 glioma cell line.
• Adiponectin enhances the sensitivity of LN18 glioma cells to temozolomide (TMZ).
• Adiponectin exhibits therapeutic promise for glioma treatment, potentially through modulation of AMPK/mTOR pathways and enhancement of chemotherapy efficacy.