An intravenous anesthetic drug-propofol, influences the biological characteristics of malignant tumors and reshapes the tumor microenvironment: A narrative literature review

Abstract

Malignant tumors are the second leading cause of death worldwide. This is a public health concern that negatively impacts human health and poses a threat to the safety of life. Although there are several treatment approaches for malignant tumors, surgical resection remains the primary and direct treatment for malignant solid tumors. Anesthesia is an integral part of the operation process. Different anesthesia techniques and drugs have different effects on the operation and the postoperative prognosis. Propofol is an intravenous anesthetic that is commonly used in surgery. A substantial number of studies have shown that propofol participates in the pathophysiological process related to malignant tumors and affects the occurrence and development of malignant tumors, including anti-tumor effect, pro-tumor effect, and regulation of drug resistance. Propofol can also reshape the tumor microenvironment, including anti-angiogenesis, regulation of immunity, reduction of inflammation and remodeling of the extracellular matrix. Furthermore, most clinical studies have also indicated that propofol may contribute to a better postoperative outcome in some malignant tumor surgeries. Therefore, the author reviewed the chemical properties, pharmacokinetics, clinical application and limitations, mechanism of influencing the biological characteristics of malignant tumors and reshaping the tumor microenvironment, studies of propofol in animal tumor models and its relationship with postoperative prognosis of propofol in combination with the relevant literature in recent years, to lay a foundation for further study on the correlation between propofol and malignant tumor and provide theoretical guidance for the selection of anesthetics in malignant tumor surgery.

Keywords: anesthetic drug; biological characteristics; chemical properties; malignant tumor; pharmacokinetic; postoperative prognosis; propofol; tumor microenvironment.

FIGURE 1

Effects of propofol on the tumor cells and tumor microenvironment. On one hand, propofol may directly act on tumor cells, exerting anti-tumor and pro-tumor effects, and regulating drug resistance. On the other hand, propofol may act indirectly on the tumor microenvironment by anti-angiogenesis, regulating immunity, reducing inflammation, and remodeling the extracellular matrix (By Figdraw).

FIGURE 2

2D and 3D chemical structure of propofol.

FIGURE 3

Metabolic process of propofol in vivo. Propofol is rapidly metabolized into inactive compounds in the liver through the hydroxylation of cytochrome P450 (CYP2B6 and CYP2C9) isomers and the UDP-glucuronosyhransferase (UGT) pathway and excreted by the kidney. Less than 1% of propofol is excreted in urine and 2% in feces.

FIGURE 4

Propofol exerts anti-tumor effects by regulating miRNAs/lncRNAs. In different tumor types, propofol regulates the expression of miRNAs (proto and anti-oncogenes) and lncRNAs to regulate different tumorigenesis and development-related signaling pathways, genes, and proteins expressions, such as PI3K/AKT, Wnt/β-catenin, MMPs, P27, and P21, thus inhibiting the proliferation, invasion, and metastasis of tumor cells, reducing EMT process and promoting apoptosis.

FIGURE 5

Effect of propofol on the tumor microenvironment. Propofol can play a role in reshaping the tumor microenvironment, including anti-angiogenesis, regulation of immunity, reduction of inflammation, and remodeling of the extracellular matrix, indirectly affecting the biological characteristics of tumor cells. Propofol can inhibit the expression of VEGF/VEGFR and play an anti-angiogenesis role. Propofol regulates immunity by affecting the infiltration and activity of a variety of immune cells, such as T cells, NK cells, and macrophages. Propofol can reduce inflammation via inhibiting the release of pro-inflammatory cytokines and targeting the expression of HMGB1 and COX-2 inflammatory proteins. In addition, propofol can target the expression of MMP-9 and ADAM8 to remodel the tumor extracellular matrix.