Table 1 Potential reagents for targeting cholesterol metabolism in HCC

HMG-CoA

Atorvastatin

Restore cholesterol-induced gut microbiome dysbiosis to inhibit lipid accumulation and HCC cell proliferation

[78]

Inhibit YAP and Akt activation to decrease prognostic liver signature score

[79]

Decrease MMP2 and MMP9 to prevent proliferation and invasiveness of HCC cells

[80]

Suppress the IL-6/STAT3 pathway to induce cellular senescence in HCC cells

[81]

Mediate TGFβ/pERK signal pathway to inhibit HCC cell proliferation and angiogenesis

[82]

Target AMPK/p21 signaling pathway to induce autophagy of HCC cells

[83]

Simvastatin

Alter the expression of cell cycle regulating proteins to induce apoptosis and cell cycle arrest

[84]

Suppress STAT3/SKP2 pathway and activate AMPK to induce cell cycle arrest

[85]

Induce HCC cells apoptosis and improve liver fibrosis and necroinflammatory score

[86]

Upregulate Notch1 expression to induce growth inhibition and apoptosis

[87]

Target HIF-1α/PPAR-γ/PKM2 axis to prevent cell proliferation and induce apoptosis, and re-sensitize HCC cells to sorafenib

[88]

SQLE

Terbinafine

Prevent Akt-mTOR signaling and upregulate PTEN expression to inhibit HCC growth

[19]

NB-598

Down-regulate TGFβ expression and SMAD2/3 phosphorylation to inhibit the viability of HCC cells

[23]

SREBP2

Betulin

Thwart the glycolytic activity to inhibit tumor growth

[90]

Target mTOR/IL-1β pathway to enhance the anti-tumor of lenvatinib

[91]

SOAT1

Avasimibe

Restrain the proliferation and migration of HCC cells

[72, 75]

Disrupt lipid homeostasis to inhibit HCC growth

[92]

LXR

TO901317

Increase REPS2 expression to inhibit proliferation and migration of HCC cells

[98]

Inhibit TGF-dependent CAF differentiation to restrict the progression of HCC

[54]

Knockdown the expression of MET and EGFR to enhance the anti-cancer activity of sorafenib

[99]

GW3965

Increase transcription level of miRNA-378a-3p to enhance anti-tumor efficacy of sorafenib

[55]

Withaferin A

Activate LXRα and inhibit the transcriptional activity of NF-κB to suppress the proliferation, migration, invasion of HCC cells

[100]

Affect Nrf2-mediated EMT and ferroptosis to prevent the metastasis and drug resistance in hepatoma cells

[102]