TABLE 5.

The anti-tumor effects of celastrol in vivo.

Cancer model (animal)	Dose and formulation	Treatment period	Tumor volume	Mechanism	Reference
HCC patient-derived xenografts (BALB/cJ mice)	4 mg/kg/day by intravenous injection	3 weeks	Reduce 2–5 fold	Pro-apoptosis, anti-proliferation through inhibited phosphorylation of protein kinases in the Raf/MEK/ERK and PI3K/AKT/mTOR signaling pathways	Wei et al. (2014)
H22 cells derived xenografts (female BALB/c mice)	1 and 2 mg/kg/day by i.p injection	3 weeks	Reduce 2–4 fold	Induced of ER stress and apoptosis	Ren et al. (2017)
Hep3B cells derived xenografts (athymic nu/nu female mice)	3 and 10 mg/kg/day by oral administration three times a week	5 weeks	Reduce 2–2.5 fold	Reduced the hypoxia-induced accumulation of HIF-1α protein, inhibited angiogenesis, invasion, and metastasis	Ma et al. (2014)
PLC/PRF5 cells derived xenografts (athymic nu/nu female mice)	1 and 2 mg/kg/day by i.p injection	3 weeks	Reduce 1.5–2.5 fold	Antiproliferative and proapoptotic effects through suppression of STAT3 signaling	Rajendran et al. (2012)
Hep3B cells derived xenografts (athymic nu/nu female mice)	2 mg/kg/day by i.p injection every 5 days	30 days	Reduce 2–2.5 fold	Inhibited circ_SLIT3/miR-223-3p/CXCR4 signaling	Si et al. (2021)
DEN induced HCC in rats	2, 4, and 8 mg/kg/day by oral administration	10 weeks	Reduce 1.5–3 fold	Activated mitochondrial apoptosis pathway	(Chang et al., 2016; Saber et al., 2020)

i.p, intraperitoneal; Raf, rapidly accelerated fibrosarcoma; ERK, Extracellular-signal-regulated kinases; MEK, Mitogen-activated protein kinase/ERK kinase; PI3K, phosphatidylinositol-3-kinase; AKT, protein kinase B; mTOR, mammalian target of rapamycin; STAT3, signal transducer and activator of transcription 3; HIF-1α, hypoxia-inducible factor, circ_SLIT3, circRNA slit guidance ligand 3; CXCR4, C-X-C motif chemokine receptor.