Impact of propofol on gastrointestinal cancer outcomes: A review of cellular behavior, growth, and metastasis

Table 1 The pharmacokinetic and pharmacodynamic properties of propofol[10]

Properties
Route of administration		Intravenous
Standard induction dose (mg/kg)		1.5-2.5
Onset of action (second)		40-60 (‘one arm brain circulation’)
Duration of action (minute)		3-10
Volume of distribution (L/kg)		5.8
Protein binding		97%-99% (mostly albumin)
Metabolism		Hepatic oxidation and conjugation to sulfate and glucuronide conjugates
Total body clearance (L/hour/kg)		3.2
Half-life	Initial (minute)	Approximately 40
	Terminal (hour)	4-7
	Context-sensitive (day)	1-3 days after a 10-day infusion. The clinical effect of propofol is much shorter
Excretion		Primarily renal

Table 2 Summary of the experimental studies of the effects of propofol on various gastrointestinal cancer cells

Ref.	Cancer cell type	Mechanism of action	Results
Miao et al[100], 2010	Colon	Inhibition of MAPKs phosphorylation including ERK1/2/JNK, P38 mainly through GABAA receptor	Inhibition of cancer cell invasion
Zhang et al[101], 2020	Colon	STAT3/HOTAIR axis by activating WIF-1; suppressing the Wnt pathway	Promotion of cell apoptosis and inhibition of cell invasion
Bai et al[104], 2021	Gastric	Up-regulation of the expression of has-miR-328-3p; down-regulation of STAT3	Inhibition of cell proliferation
Wang et al[105], 2023	Colon	Down-regulation of SIRT1; inhibition of the Wnt/β-catenin pathway and PI3K/AKT/mTOR pathway	Inhibition of stemness and cell proliferation
Zhan et al[109], 2023	Gastric	Induction of miR-493-3p via targeting DKK1; inhibition of Wnt/β-catenin signaling	Inhibition of the growth and invasion of cells
Alexa et al[110], 2023	Colon	Increased expression of TP53 gene	No influence on apoptosis, migration, and cell cycle
Xu et al[112], 2018	Colon	Induction of IL-13; suppression the expression of STAT6 and inhibition of IL-13/STAT6/ZEB1 signaling pathway through up-regulation of miR-361 and miR-135b	Inhibition of EMT, invasion and cell proliferation
Liu et al[113], 2020	Gastric	Promotion of miR-195-5p expression; suppression of Snail expression	Inhibition of EMT, invasion, and migration of cells
Zhao and Liu[114], 2021	Colon	Knockdown of circ-PABPN1; upregulation of miR-638; downregulation of SRSF1 expression	Repression in cell viability, colony formation, invasion, migration, and promotion in apoptosis
Wu et al[115], 2022	Colon	Upregulation of caspase 3; inhibition in glycolytic pathway with suppression LDH	Reduction in cell viability, migration, and invasion
Li et al[116], 2020	Colon	Upregulation of miR-124-3p.1; downregulation of AKT3 expression	Suppression of proliferation, invasion, and metastasis of cells
Yao et al[117], 2024	Colon	Regulating FOXO1-mediated transcription of LINC01133; promotion NR3C2 expression through miR-186-5p sponging	Inhibitory effect on cell progression and tumor metastases
Ye et al[118], 2021	Colon	Promoting miR-1-3p; inhibition of IGF-1 expression through interacting with its 3’-UTR; inactivating AKT/mTOR signals	Suppression of cell proliferation and promotion of apoptosis
Xian et al[120], 2020	Stomach	Overexpressing of miR-205; inhibiting the YAP1 axis	Inhibition of cell growth; promotion of apoptosis
Iwasaki et al[121], 2023	Colon	Decrease in HIF1α, IL1β, HGF gene expressions; increase in TIMP-2 gene and protein expression	Reduction in tumor size
Chen et al[122], 2018	Colon	Depression of the NMDAR-CAMKII-ERK pathway and consequent inhibition of HIF1α; inhibition of the expression of GLUT1, HK2, PGK1, and LDHA enzymes	Dose-dependent decrease in aerobic glycolysis (Warburg effect)
Gao et al[123], 2021	Colon	Inhibition of the expression of miR-155, TLR4/NF-κB	Promotion of the expression of tight junction protein in the intestinal mucosa; protection of the intestinal barrier; prevention of the translocation of intestinal bacteria; increase in the level of beneficial Lactobacillus bacteria on the mucosal surface
Liu et al[124], 2018	Colon	Positive expression of GranB and Ki67; increased release of LDH	Increase in the number of NK cells; promotion of the activation, proliferation ability, and killing effects of NK cells
Zhou et al[125], 2018	Esophagus	Increase in the expression of granzyme B and IFN-γ	Promotion of the proliferation and functional capacity of NK cells
Ai and Wang[126], 2020	Gastric	Inhibition of the negative regulation of gastric cancer cells and TGF-1; SMAD4 pathway by upregulating the expression of granzyme B	Increase the cytotoxicity and killing functions of NK cells

MAPKs: Mitogen-activated protein kinases; ERK: Extracellular signal-regulated kinase; JNK: c-Jun NH2-terminal kinase; GABAA: Gamma-aminobutyric acid subtype A; STAT3: Signal transducer and activator of transcription 3; HOTAIR: HOX antisense intergenic RNA; WIF-1: Wnt-inhibitory factor-1; PI3K: Phosphatidylinositol-3-kinase; AKT: Protein kinase B; mTOR: Mammalian target of rapamycin; DKK1: Dickkopf-1; IL: Interleukin; SRSF1: Serine/arginine-rich splicing factor 1; LDH: Lactate dehydrogenase; FOXO1: Forkhead box O1; NR3C2: Nuclear receptor subfamily 3 group C member 2; IGF-1: Insulin-like growth factor 1; UTR: Untranslated region; YAP1: Yes-associated protein 1; HIF: Hypoxia-inducible factor; HGF: Hepatocyte growth factor; TIMP-2: Tissue inhibitor metalloproteinase 2; NMDAR: N-methyl-D-aspartate receptor; CAMKII: Calcium-calmodulin-dependent protein kinase II; GLUT1: Glucose transporter type 1; HK2: Hexokinase 2; PGK1: Phosphoglycerate kinase 1; LDHA: Lactate dehydrogenase A; TLR4: Toll-like receptor 4; NF-κB: Nuclear factor kappa B; IFN: Interferon; TGF: Transforming growth factor; EMT: Epithelial-mesenchymal transition; NK: Natural killer.

Table 3 A summary of the clinical studies

Ref.	Cancer type	Compared anesthetics/study type	Results
Wu et al[127], 2018	Colon	Propofol vs desflurane/retrospective cohort	Propofol anesthesia is associated with better overall survival, less local recurrence, less postoperative metastasis
Zhang et al[128], 2022	Digestive tract	Propofol vs volatile anesthetics (isoflurane, desflurane, sevoflurane)/retrospective cohort	The selection of anesthetic agents does not affect survival and postoperative complication(s)
Hasselager et al[129], 2022	Colorectal	Propofol vs sevoflurane/retrospective cohort	No difference regarding medical complications; better rates of surgical complications for the sevoflurane group
Kagawa et al[130], 2024	Gastric	Propofol vs volatile anesthetics (isoflurane, desflurane, sevoflurane)/retrospective cohort	No significant overall survival between groups
Ma et al[131], 2023	Esophageal	Propofol vs sevoflurane/retrospective observational	No significant difference in overall survival and disease-free survival between groups
Margarit et al[132], 2014	Colorectal	Propofol vs isoflurane/randomized controlled	No significant differences between groups on plasma concentrations of IL-6 and IL-10
Xu et al[134], 2016	Colon	Propofol + thoracic epidural vs sevoflurane	A reduction in invasiveness, proliferation, and metastatic potential, as well as enhanced apoptosis of the cancer cells in propofol group
Buschmann et al[135], 2020	Colorectal	Propofol vs sevoflurane/proof-of-concept	Propofol-regulated miRNAs might mediate inhibitory effects on signaling pathways involving cell proliferation, migration, and epithelial-mesenchymal transition of tumor cell lines and enhance effects on apoptosis of carcinoma cell lines
Oh et al[136], 2022	Colorectal	Propofol vs sevoflurane/randomized controlled	The type of general anesthetics used may minimally affect perioperative immune status among numerous perioperative factors
Kim et al[137], 2021	Gastric	Propofol vs sevoflurane	Propofol is superior for the protection of endothelial glycocalyx; similar effects on endothelial glycocalyx degradation and inflammatory process
Zhang et al[138], 2024	Colorectal	Propofol vs sevoflurane/retrospective observational	Propofol exhibited superior survival outcomes among individuals with a high degree of PNI change

IL: Interleukin; miRNA: MicroRNA; PNI: Prognostic nutritional index.