Research progress of hyperthermia in tumor therapy by influencing metabolic reprogramming of tumor cells

Figures & data

Figure 1. The most notable metabolic modalities of tumor cells include mainly glucose metabolic reprogramming, lipid metabolic reprogramming and amino acid metabolic reprogramming. They play an important role in tumor progression and cover a wide range of aspects including tumor proliferation, distant metastasis, death resistance, immune evasion and treatment tolerance.

Figure 2. Thermotherapy affects other therapeutic modalities such as chemotherapy, radiotherapy, immunotherapy, sonodynamic therapy and photodynamic therapy by influencing the critical metabolic modalities or metabolites involved in the reprogramming of glucose, lipid and amino acid metabolism.

Table 1. Changes in each metabolite or metabolic process under the influence of hyperthermia alone.

	Metabolite/Metabolic process	Temperature	Time	Models/Cells	Effects
Glucose metabolism	PKM2	39.6o	5min	Nude mice bearing orthotopic MCF-7 tumors	PKM2 began to show a decreasing trend and decreased significantly with the increase in temperature.
	GLUT-1	42U	2h	Bovine aortic endothelial cells	Reduction in GLUT-1 and glucose uptake.
Lipid metabolism	VLDL	patent protection		WAG rat with Walker 256 tumors	Increase in VLDL and increase in survival of rats.
	ACC	43C	10min	HCC-LM3、Hep-G2 cells	Decrease in P-ACC and increase in apoptosis.
	Lipid raft	42p	60min	B16(F10) cells	Reorganization of membrane cholesterol and removal of lipid rafts.
Amino acid metabolism	Glutamine	44u	33min	Balb/c 3T3 cells	Increase in glutamine concentration and expression of HSPs.
	Glutathione	40u	60min	Hela cells	Elevation of glutathione levels and increase in apoptosis.
Mitochondria	HIF-1	43F	60min	4T1 mouse with mammary carcinoma cells	Increase in HIF-1 and decrease in oxygen consumption.
	oxidative phosphorylation	42i	15min	Male Wistar rats	Significant inhibition of the respiratory chain components and progressive impairment of oxidative phosphorylation.
	Oxygen consumption	46i	5min	Human pancreatic cancer cell lines	Downregulation of mitochondrial membrane potential and decrease in oxygen consumption rate.
	Cytochrome C	43t	3h	L929 cells	Increase in cytochrome C and activation of the mitochondrial apoptotic pathway.
Other	Cer	42r	60min	NIH WT-3T3 cells	Formation of "Cer-raft" by Cer replacing Chol and reduction in the stability of the membrane structure of tumor cells.
	P2X7 pore	40X	30min	MCA38 wild type cells	Increase in P2X7 pore and activation of cell death pathway.
	ROS	44S	30min	Human myelomonocytic lymphoma U937 cells	Accumulation of ROS and activation of apoptosis.
	ATP/PME	41.5P	100min	Canines with soft tissue sarcomas	ATP/PME decreases and the reduction in ATP/PME predicted for a greater degree of tumor necrosis.

Data availability statements

Data availability is not applicable to this article as no new data were created or analyzed in this study.