[NCTD Retards AML HL60 Cell Proliferation via Targeting Hedgehog/SOX2 axis]

Area of Science:

• Oncology
• Molecular Biology
• Pharmacology

Background:

• The sonic Hedgehog (SHH) pathway plays a role in cell proliferation and is implicated in various cancers, including leukemia.
• SOX2 is a transcription factor downstream of the SHH pathway, often overexpressed in cancers.
• Norcantharidin (NCTD) is a derivative of cantharidin with potential anti-cancer properties.

Purpose of the Study:

• To investigate the effect of norcantharidin (NCTD) on leukemia cell proliferation.
• To determine if NCTD disrupts the sonic Hedgehog (SHH) pathway and its downstream target SOX2.
• To explore the role of the SHH/SOX2 axis in NCTD's anti-leukemic activity.

Main Methods:

• Cell Counting Kit-8 (CCK8) assays were used to assess the proliferation of HL60 and NB4 leukemia cells.
• Western blotting was employed to detect protein expression levels of SMO, GLI1, and SOX2 after NCTD treatment.
• HL60 cells were genetically modified to overexpress GLI1 or SOX2 to study their impact on proliferation and NCTD resistance.

Main Results:

• NCTD and inhibitors of SMO/GLI1 significantly inhibited HL60 and NB4 cell proliferation in a dose-dependent manner.
• NCTD treatment led to a remarkable decrease in the protein levels of SMO, GLI1, and SOX2 in HL60 cells.
• Overexpression of GLI1 or SOX2 in HL60 cells conferred a proliferative advantage and increased resistance to NCTD treatment.

Conclusions:

• Norcantharidin (NCTD) effectively attenuates leukemia cell proliferation.
• NCTD exerts its anti-leukemic effect by targeting the Hedgehog/SOX2 signaling axis.
• The SHH/SOX2 pathway is a critical regulator of leukemia cell growth and response to NCTD.