TABLE 2.

Summary of the antitumor effects of celastrol and chemotherapeutic drugs in vivo.

Treatment	Type of cancer	Animal model	Findings	Ref
Carboplatin	PHGG	Female athymic nude mice were stereotactically injected VUMC-HGG-14 cells (50 × 104 cells in 5 μL) into the striatum	Prolong survival of pHGG-bearing mice; combination therapy using celastrol and carboplatin might serve as a clinically relevant strategy for the treatment of pHGG	(Metselaar et al., 2019)
Bortezomib	Multiplemyeloma	Male athymic balb/c nude mice were implanted with 2 × 106 cells with human MM U266 cell lines subcutaneously	Augmented bortezomib induced inhibition of tumor growth; No any obvious side effects	(Shanmugam et al., 2018)
EGFR-TKIs	Lung cancer	BALB/c nude mice were subcutaneously injected with 2 × 106 H1975 lung carcinoma cells	Inhibit tumor growth	(Wang et al., 2018)
SAHA	Lung cancer	Human lung cancer 95-D xenografts were established by subcutaneously inoculating 5 × 106 cells into nude mice	Tumor growth inhibition without increased toxicity	(Zheng et al., 2014)
Sorafenib	Liver cancer	The C57bl/6 mice were injected subcutaneously with Hepa1-6 single-cell suspension cells (2 × 107/ml) into the right flank	Enhance the antitumor activity and reduce the dosage of sorafenib	(Zhang et al., 2019)
PHA-665752	Liver cancer	Male nude mice were inoculated subcutaneously with human liver cancer cell lines Huh7	The combination of celastrol and PHA could effectively inhibit c-met-deficient hepatocellular carcinoma cells growth, migration and apoptosis	(Jiang et al., 2013)
Trastuzumab, Lapatinib	Breast cancer	Female NODSCID mice received sub-cutaneous 17β-estradiol pellet (0.72 mg/day), 2 weeks prior to injection of 5 x 106 BT-474 cells resuspended in 4% Matrigel	Retard the rate of growth of ErbB2- overexpressing human breast cancer cells in a mouse xenograft model with only minor systemic toxicity	(Raja et al., 2011)
X66	Breast cancer	Female Balb/cA-nude mice were implanted subcutaneously with BT-474 cells in the right flank	Enhance anti-tumor activity, with no additional toxicity	(Zhao et al., 2016)
TRAIL/APO-2L	Lung cancer	Human lung cancer 95-D xenografts were established by 5 × 106 cells subcutaneously inoculated in nude mice	Increase the in vivo antitumor capacities without increasing the toxicities caused by the celastrol	(Zhu et al., 2010a)
TRAIL/APO-2L	Colon cancer	Human colon cancer SW620 xenografts were established by 5 × 106 cells subcutaneously inoculated in nude mice	Inhibit tumor growth	(Zhu et al., 2010b)
Triptolide	Lung cancer	Balb/c nude mice were injected subcutaneously with H1299 or H157 cells (3 × 106 in 100 μL of medium) under the shoulder	Inhibit the growth of tumors without obvious toxicity	(Jiang et al., 2015)
Ellagic acid	Lung cancer	Female BALB/C nude mice were injected HOP62 cells (1 × 106) subcutaneously into the right rear flank	Inhibitory effects on tumor growth, without a reduction in body weight	(Duan et al., 2019)
miR-33a-5p	Lung cancer	BALB/c-nu/nu male mice were injected subcutaneously with LTEP-a-2 cells into the right or left flanks	miR-33a-5p inhibited the proliferation of lung adenocarcinoma cells, enhanced the antitumor effect of celastrol, and improved sensitivity to celastrol by targeting mTOR	(Li Y. J. et al., 2018)
Ionizing radiation	Prostate cancer	Female athymic NCr-nu/nu mice were inoculated subcutaneously on both sides of the lower back above the tail with 3 × 106 cells/0.2 ml of PC-3 cells	Inhibit PC-3 tumor growth without obvious systemic toxicity	(Dai et al., 2009)
Ionizing radiation	Lung cancer	Nude mice were injected with 5 × 107 A549 cells in the back subcutaneously	Radiosensitizing agent celastrol has therapeutic effects when combined with ionizing radiation	(Jun et al., 2017)

EGFR-TKI, epidermal growth factor receptor tyrosine kinase inhibitor; SAHA, suberoylanilide hydroxamic acid; TRAIL/APO-2L, tumor necrosis factor (TNF) α–related apoptosis-inducing ligand; X66, 4-(2-((1H-indol-3-yl)methylene)hydrazinyl)-N-(4-bromophenyl)-6-(3,5- dimethyl-1H -pyrazol-1-yl)-1,3,5-triazin-2-amine.