Role Of Propofol Research Articles

The Role of Propofol in Alcohol Withdrawal Syndrome: A Systematic Review.

The objective of this review was to evaluate the efficacy and safety of propofol in the treatment of critically ill patients diagnosed with alcohol withdrawal syndrome (AWS). A review was conducted in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) criteria, and Embase, MEDLINE (PubMed), Cochrane CENTRAL, and Web of Science were queried for results through June 2024. Studies providing efficacy or safety data associated with propofol with a reported diagnosis of AWS in critically ill patients were included. Studies evaluating pediatric patients, those without quantitative and qualitative outcome data, and those not readily translatable to English were excluded. Five retrospective cohort analyses of 218 patients were included in this systematic review. Patients were found to have both significant and non-significant increases in time to resolution of AWS symptoms when treated with propofol versus the AWS standard of care. Adjunct treatment with propofol was generally associated with reductions in total benzodiazepine use and increases in both ICU length of stay and duration of mechanical ventilation. The results of this systematic review provide the evidence necessary to support the use of propofol as an efficacious and safe medication in the management of severe and refractory AWS. Further investigation is required to determine optimal dosing strategies and durations of therapy. The results of this systematic review demonstrate the clinical utility of propofol as part of the management strategy for severe and refractory AWS.

The Effects of Propofol on Efflux Activity in Alzheimer’s Disease Human Stem Cell-Derived Blood-Brain Barrier Models

Propofol is a common induction anesthetic that recently has been shown to diminish the integrity of the blood brain barrier (BBB) while maintaining efflux protein expression and activity. Furthermore, Alzheimer’s disease (AD), a neurodegenerative condition, compromises the integrity of the BBB including suppressed efflux activity. Efflux transporters, notably MRP-1, BCRP, and P-gp, play a role in clearing cytotoxic metabolites. The role of propofol on the activity of efflux proteins in AD patients is unknown. The goal of this study was to utilize human induced pluripotent stem cell (iPSC)-derived brain microvascular endothelial cells (BMECs) differentiated from familial AD iPSCS (APP, PSEN1, and PSEN2) and healthy iPSCs to determine the effects of propofol on efflux activity and expression.To measure the effect of propofol on efflux activity, treated cells were exposed to 50μM propofol for three hours and then specific efflux fluorescent substrates and inhibitors were utilized to determine efflux activity ( P-gp: Rhodamine 123/CsA; MRP-1: DCFDA/MK571; BCRP: Hoechst/KO143). Cells were lysed and the fluorescent substrate was quantified by a plate reader and normalized to the uninhibited group. The difference between the inhibited and uninhibited groups were used to determine the efflux activity. Efflux protein expression was also qualitatively assessed using immunostaining.Our preliminary results demonstrated that propofol did not affect efflux activity similar to previous literature. Interestingly, PSEN 1 and PSEN2 had suppressed baseline efflux transporter activity and did not show any change following propofol exposure. APP-derived BMECs displayed suppressed P-GP activity and similarly to PSEN 1/2-derived BMECs were not altered by propofol. Our preliminary results implicate that AD-derived BMECs have suppressed baseline efflux activity; however propofol exposure did not further alter activity level. Additional studies are needed to determine the role of anesthesia-induced injury on efflux activity and expression.

Propofol maintains Th17/Treg cell balance in elderly patients undergoing lung cancer surgery through GABAA receptor

Propofol is widely used in clinical anesthesia due to its advantages of rapid onset and less adverse reactions. This study focused on the role of propofol in the balance of Th17/Treg in elderly patients with lung cancer during perioperative period. Patients undergoing lung cancer surgery were anesthetized by propofol or sevoflurane. Veinal blood was collected at different time points to evaluate the changes of Th17/Treg cell. Propofol better maintained the balance of Th17/Treg in vivo. The peripheral blood of patients with lung cancer was collected in vitro before surgery. Cluster of differentiation (CD)4+ T cells were obtained and then treated with propofol at different concentrations and γ-aminobutyric acid A (GABAA) receptor antagonists. Propofol affected Th17/Treg cell balance by increasing Th17 cells, decreasing Treg cells, thus elevating Th17/Treg ratio, and inhibited invasion and migration of lung cancer cells through GABAA receptor, which was counteracted by GABAA receptor inhibitors. Subsequently, tumor in situ model of lung cancer in aged mice was established. Propofol anesthetized mice had lower change of Th17/Treg ratio, higher survival rate and less metastasis. In brief, propofol regulated balance of Th17/Treg in elderly patients undergoing lung cancer surgery through GABAA receptor. Additionally, propofol could inhibit metastasis of lung cancer.

Role of Propofol with total intravenous anesthesia in intra-abdominal surgeries

The analgesic properties of propofol may make it a useful opioid-sparing analgesic adjunct for colorectal surgery in the context of a multimodal analgesic regime. Propofol is a commonly used intravenous anesthetic drug. Total intravenous anesthesia (TIVA) with propofol can be used for both induction and maintenance of general anesthesia. Propofol has been associated with pain relief both in animal studies and in human healthy volunteer studiesPostoperative pain can be severe post multiple abdominal surgeries due to the upper abdominal incision and pain management can be difficult for this group of patients,therefore total intravenous anaesthesia is a technique involving infusion and maintenance of anaesthetic state with intravenous drugs alone. But no agent has all the characteristics of ideal TIVA agent. Propofol has three important characteristics of ideal TIVA agent, i.e. rapid induction, rapid metabolism and rapid recovery. In this communication we studied the characteristics of propofol in total intravenous anaesthesia in various intra-abdominal surgeries. Vital signs, including blood pressure, oxygen saturation (SpO2), heart rate, and body temperature, were monitored in the post anesthesia care unit (PACU).

Effect of Propofol and Dexmedetomidine on Pulmonary Injury in Patients with Acute Respiratory Distress Syndrome during Mechanical Ventilation

Objective: This research intended to explore the role of propofol and dexmedetomidine on pulmonary injury in patients with acute respiratory distress syndrome (ARDS) during mechanical ventilation. Methods: A total of 150 ARDS patients undergoing mechanical ventilation in our hospital from January 2017 to May 2019 were randomly grouped into dexmedetomidine group (n=50), propofol group (n=50) and joint group (n=50). The changes of heart rate, systolic blood pressure, diastolic blood pressure in the three groups were compared. Elisa was applied to test the changes of inflammatory factors interleukin-6 (IL-6) and tumor necrosis factor-a (TNF-a) on the first, second and third days after mechanical ventilation. The pulmonary injury score before sedation and after sedation for 2 days (Table 2) was tested. Secondary outcome measures: the incidence of adverse reactions after anesthesia was observed. Results: After sedation, the mean artery pressure and heart rate of the three groups were significantly lower than those before sedation (P < 0.05). After sedation, the expressions of IL-6 and TNF-a in joint group were significantly lower than those in propofol and dexmedetomidine group (P < 0.05). Two-day pulmonary injury scores of the three groups showed that different sedation schemes had positive effects on improving pulmonary injury scores (P < 0.05), and the expressions of IL-6 and TNF-a declined with the decline of pulmonary injury scores. The incidence of adverse reactions in joint group was significantly higher than that in propofol group and dexmedetomidine group (P < 0.05). Conclusion: Propofol and dexmedetomidine can effectively improve the effect of pulmonary injury in ARDS patients during mechanical ventilation, and slow down the occurrence of inflammatory reaction, which is an effective scheme of sedation in clinical mechanical ventilation.

Propofol Suppresses Cell Progression by Inhibiting CCL18 Expression in Hepatoblastoma

Background Propofol is an anesthetic commonly used clinically and has been found to have antitumor activity in various cancers. The purpose of this study was to investigate the role of propofol in hepatoblastoma (HB). Methods CCK-8 and transwell were used to measure cell proliferation, migration, and invasion in HB cells. Cell apoptosis rate was measured by FCM. The expression of CCL18 in HB tissues and cells was detected by RT-qPCR. Western blotting was used to explore the protein expression of CCK18- and PI3K/AKT-related proteins. Results The expression of CCL18 in HB tissues and cells was overexpressed compared with control groups. CCL18 knockdown was found to notably block cell proliferation and progression, while enhancing cell apoptosis in HuH-6 and HepT1 cells. Furthermore, propofol suppressed the proliferation of HB cells in a dose-dependent manner. According to the results, we chose 5 μg/mL of propofol-treated cells for 48 hours as the subsequent experimental conditions. We found that propofol (5 μg/mL, 48 h) significantly blocked cell migration and invasion, but induced cell apoptosis in HuH-6 and HepT1 cells. In addition, CCK18 overexpression facilitated cell progression in HB cells, while propofol dramatically suppressed the effect of CCK18. Besides that, propofol suppressed the PI3K/AKT pathway. Conclusion Propofol suppressed the development of HB cells by inhibiting CCK18 expression and the PI3K/AKT pathway. Therefore, we infer that propofol plays a role in the treatment of HB.

Propofol ameliorates neuropathic pain and neuroinflammation through PPAR γ up-regulation to block Wnt/β-catenin pathway

ABSTRACT Objective As an intravenous anesthetic, propofol has been exhibited to provide excellent clinical analgesia. Whether propofol has amelioration property for NP and neuroinflammation remains unexplored. The present study was arranged to probe the role of propofol in the mitigation of NP and neuroinflammation in rats and underlying mechanisms. Methods Rats were randomly classified into the following groups: Model, Sham, Control, Propofol, GW9662, and Saline groups. The radiant heat stimulation was used to measure paw withdrawal latency (PWL), and mechanical stimulation was employed to detect paw withdrawal threshold (PWT). Subsequently, the expression of GFAP was assessed by immunofluorescence to reflect the activation of astrocyte. qRT-PCR and Western blot were utilized for the performance of mRNA and protein expression levels of PPAR γ as well as inflammation factors (TNF-α, IL-1β, and IL-6). Results Pentobarbital sodium anesthesia significantly shortened the PWL and PWT, suppressed PPAR γ expression in rats in addition to elevating astrocyte activation and inflammation response. Propofol treatment attenuated the NP of rats as evidenced by restrained astrocyte activation level and inflammation factor levels. Rats treated with propofol had markedly heightened PPAR γ expression. PPAR γ exposure ameliorated NP and inflammation degree, which demonstrated by elevated astrocyte activation and inflammation levels as well as suppressed PWL and PWT in rats injected with PPAR γ inhibitor. Besides, PPAR γ decreased the expression level of β-catenin. Conclusion Propofol ameliorates NP and neuroinflammation of rats by up-regulating PPAR γ expression to block the Wnt/β-catenin pathway.

Role of propofol with total intravenous anesthesia in intra-abdominal surgeries: A prospective study

Background: Postoperative pain can be severe post multiple abdominal surgeries due to the upper abdominal incision and pain management can be difficult for this group of patients, therefore total intravenous anaesthesia is a technique involving infusion and maintenance of anaesthetic state with intravenous drugs alone. But no agent has all the characteristics of ideal TIVA agent. Propofol has three important characteristics of ideal TIVA agent, i.e. rapid induction, rapid metabolism and rapid recovery. In this communication we studied the characteristics of propofol in total intravenous anaesthesia in various intra-abdominal surgeries. Methods: Here our sample size was 52 patients aged 18 to 60 years belonging to ASA gr 1 and gr 11 undergoing various elective intra- abdominal surgery took part in this prospective study. All patients were induced with 2mg/kg body weight 1% propofol after premedication 0.03 mg midazolam and pentazocine. Anesthesia maintained with 0.1% propofol at rate of 100Ug/kg/min with 100% oxygen and incremental dose muscle relaxant. Based on haemodynamic sings and sympathetic over activity dose of propofol was adjusted in intraoperative period. At skin closure infusion was discontinued and neuromuscular blockade reversed. Result: In our results, TIVA with propofol enabled smooth and rapid induction in all patients with induction time of 29.7 seconds. In maintenance phase propofol provides adequate depth of anaesthesia assessed by haemodynamic changes and sympathetic over activity in 47 (92%) of the patients. Five patients (8%) needed higher dose of infusion to maintain adequate depth of anaesthesia. Recovery was good with short response time of 10.3 minutes and orientation time of 14.54 minutes. Conclusion: Our study concludes like others, Propofol based TIVA provides smooth and rapid induction and acceptable haemodynamic status during maintenance period in most of the patients. All patients were alert and clear headed with smooth recovery from anaesthesia effect.

Propofol suppresses the progression of non‑small cell lung cancer via downregulation of the miR‑21‑5p/MAPK10 axis.

Non-small cell lung cancer (NSCLC) accounts for >80% of lung cancer cases and is the leading cause of cancer-associated mortality worldwide. Propofol is an anesthetic drug frequently used during tumor resection. It is also known to exert inhibitory effects on cancer. Although the role of propofol in NSCLC has been reported, its underlying mechanisms remain unknown. The present study aimed therefore to investigate the mechanisms of propofol action on NSCLC. Starbase V3.0 project was used to analyze the expression levels of microRNA-21-5p (miR-21-5p) and mitogen-activated protein kinase 10 (MAPK10) in NSCLC and adjacent normal tissues from patients with NSCLC and the association between miR-21-5p and MAPK10 expression level in NSCLC tissues. The correlation between MAPK10 expression and disease-free survival (DFS) in patients with NSCLC was analyzed using GEPIA software version 1.0. miR-21-5p and MAPK10 expression in tumor and adjacent normal tissues from patients with NSCLC was evaluated by reverse transcription-quantitative (RT-q) PCR and western blotting. Cell viability and apoptosis were assessed by using Cell Counting Kit-8 assay and flow cytometry, respectively. The interaction between miR-21-5p and MAPK10 was predicted by TargetScan/miRanda and verified by dual luciferase assay. The regulatory effect of propofol on miR-21-5p and MAPK10 expression in NSCLC cell lines was examined by RT-qPCR and western blotting. Starbase V3.0 project and the results of the present study indicated that tumor tissues presented a significantly lower MAPK10 level and a higher miR-21-5p level compared with the normal samples, and that miR-21-5p expression was negatively correlated with MAPK10 expression in the tumor tissues of patients with NSCLC. Furthermore, miR-21-5p targeted the 3′-untranslated region of MAPK10. In addition, compared with BEAS-2B cells, a higher miR-21-5p and a lower MAPK10 expression was observed in the NSCLC cell lines A549 and H1299, which was reversed by propofol. The overexpression of miR-21-5p abrogated the effects of propofol on A549 and H1299 cell viability and apoptosis by targeting MAPK10. Taken together, these findings demonstrated that propofol inhibited the viability and promoted the apoptosis of NSCLC cells by downregulating the miR-21-5p/MAPK10 axis.

Propofol suppresses migration, invasion, and epithelial-mesenchymal transition in papillary thyroid carcinoma cells by regulating miR-122 expression.

Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer and PTC patients with invasion and metastases features have a poor prognosis. Propofol is an intravenous anesthetic which has been reported to be involved in cancer progression. However, the roles of propofol and the exact molecular mechanisms in PTC remain largely unknown. Cells viability was detected using the CCK-8 (Cell Counting Kit-8) assay. The expressions of microRNA-122 (miR-122) were measured by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Cells migration and invasion abilities were investigated by transwell. Western blot was used to demonstrate the expression of metastasis-and EMT-related proteins. We found a significant inhibition of cells viability in TPC-1 and IHH-4 cells compared to Nthy-ori 3-1 cell line after exposed to propofol. The functional experiment showed propofol could suppress cells migration, invasion, and EMT in PTC. Subsequently, a decreased expression of miR-122 was detected in TPC-1 and IHH-4 cells, while a promotion of propofol on miR-122 expression was identified. Furthermore, we found miR-122 could inhibit cells migration, invasion, and EMT in PTC. Next, the rescue study indicated that miR-122 inhibitor transfection could attenuate propofol-induced suppression on TPC-1 and IHH-4 cells metastasis. Propofol suppresses migration, invasion, and EMT in papillary thyroid carcinoma cells by regulating miR-122 expression. The findings may indicate significant clinical implications for anesthetic agents to prevent metastasis and improve outcomes in papillary thyroid carcinoma.

Propofol suppresses proliferation and metastasis of colorectal cancer cells by regulating miR-124-3p.1/AKT3.

Propofol, an extensively used intravenous anesthetic agents during cancer resection surgery, has been confirmed to execute anti-tumor effect on multiple cancers, including colorectal cancer (CRC). Although the role of propofol in CRC has been previously reported, its action mechanism remains poorly understood. This study further explored the biological function and underlying mechanism of propofol in CRC cells. The cell proliferation, migration and invasion were assessed by methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay, wound healing assay and transwell assay, respectively. The expression levels microRNA-124-3p.1 (miR-124-3p.1) and AKT serine/threonine kinase 3 (AKT3) was analyzed by quantitative real-time polymerase chain reaction. Western blot assay was employed to measure the protein expression of MMP-9, Vimentin and Cyclin D1. The interaction between miR-124-3p.1 and AKT3 was predicted by TargetScan and confirmed by dual-luciferase reporter assay. Propofol inhibited CRC cell proliferation, migration and invasion. Knockdown of miR-124-3p.1 or AKT3 upregulation reversed the inhibitory effects of propofol on CRC cell proliferation and metastasis. Besides, AKT3 was a direct target of miR-124-3p.1 and its overexpression abated the anti-tumor effect of miR-124-3p.1 on CRC cell proliferation and metastasis. Propofol inhibited CRC cell proliferation, migration and invasion by upregulating miR-124-3p.1 and downregulating AKT3, providing a new sight for propofol treatment of CRC.

Propofol exhibits a tumor-suppressive effect and regulates cell viability, migration and invasion in bladder carcinoma by targeting the microRNA-10b/HOXD10 signaling pathway.

2,6-diisopropylphenol (propofol) is a commonly used intravenous anesthetic drug, which has been reported to serve an antitumor role in human cancers. The current study aimed to assess the effects of propofol on the biological behaviors of human bladder cancer cells and to elucidate its potential molecular mechanism. The results of MTT, wound healing and Matrigel invasion assays demonstrated that propofol significantly inhibited the viability, migration and invasion of bladder cancer T24 cells in vitro. Reverse transcription-quantitative PCR and western blotting revealed that propofol decreased the expression levels of microRNA (miR)-10b and increased the expression levels of homeobox D10 (HOXD10) in T24 cells. Luciferase reporter assay revealed that HOXD10 was a direct target of miR-10b in T24 cells. T24 cells transfected with a miR-10b mimic significantly reduced the mRNA and protein expression levels of HOXD10. In addition, overexpression of miR-10b partly reversed the inhibitory effect of propofol on T24 cell viability, migration and invasion induced by upregulation of HOXD10. In summary, the present study focused on the role of propofol in the treatment of bladder cancer and demonstrated that propofol may serve a tumor-suppressive role and control cell viability, migration and invasion of T24 cells by targeting the miR-10b/HOXD10 signaling pathway, which indicated that propofol may be used as an effective therapeutic drug for the treatment of bladder cancer.

Cox-2 Negatively Affects the Protective Role of Propofol against Hypoxia/Reoxygenation Induced Cardiomyocytes Apoptosis through Suppressing Akt Signaling.

Nowadays, the prevention of severe myocardium injury resulting from myocardial ischemia/reperfusion injury (I/R) has been recognized as an important subject in the field of ischemic heart disease. In this study, H9c2 cardiomyocytes were exposed to cycles of hypoxia/reoxygenation (H/R) to mimic myocardial I/R injury. Western blot analysis and qRT-PCR were performed to detect the expression of Cox-2, Akt and p-Akt. Cell viability, LDH release and activity of Caspase-3 were assessed to determine the protective effect of propofol. The results proved that the protective effect of propofol for H/R challenged cardiomyocytes was associated with Akt phosphorylation. We also revealed that treatment of propofol suppressed the expression of Cox-2 in cardiomyocytes which was up-regulated after H/R treatment. Conversely, the over-expression of Cox-2 inhibited Akt phosphorylation while enhancing cardiomyocytes apoptosis. Interestingly, Akt activator exhibited similar protective effect with propofol and could diminish the influences brought by over-expression of Cox-2. Thus, it could be concluded that Cox-2 negatively affects the protective effect of propofol against hypoxia/reoxygenation induced cardiomyocyte apoptosis by suppressing Akt phosphorylation.

RETRACTED ARTICLE: Propofol suppresses growth, migration and invasion of A549 cells by down-regulation of miR-372

BackgroundPropofol, a commonly used intravenous anesthetic during cancer resection surgery, has been found to exhibit tumor inhibitory effects in vitro and in vivo. The role of propofol in lung cancer has been previously reported, whereas its action mechanism remains unclear. This study further investigated the effects of propofol on lung cancer A549 cell growth, migration and invasion, as well as the underlying mechanisms.MethodsCell viability, proliferation, migration, invasion and apoptosis were assessed by CCK-8 assay, BrdU assay, two chamber transwell assay and flow cytometry, respectively. The regulatory effect of propofol on microRNA-372 (miR-372) expression in A549 cells was analyzed by qRT-PCR. Cell transfection was used to change the expression of miR-372. The protein expression of key factors involving in cell proliferation, apoptosis, migration and invasion, as well as Wnt/β-catenin and mTOR pathways were analyzed by western blotting.ResultsPropofol inhibited lung cancer A549 cell viability, proliferation, migration, and invasion, but promoted cell apoptosis. Moreover, miR-372 was down-regulated in propofol-treated A549 cells. Overexpression of miR-372 abrogated the effects of propofol on proliferation, migration, invasion and apoptosis of A549 cells. Knockdown of miR-372 had opposite effects. Furthermore, propofol suppressed Wnt/β-catenin and mTOR signaling pathways by down-regulating miR-372.ConclusionPropofol inhibits growth, migration and invasion of lung cancer A549 cells at least in part by down-regulating miR-372 and then inactivating Wnt/β-catenin and mTOR pathways.

Propofol alleviates hypoxia-induced nerve injury in PC-12 cells by up-regulation of microRNA-153

BackgroundAlthough the neuroprotective role of propofol has been identified recently, the regulatory mechanism associated with microRNAs (miRNAs/miRs) in neuronal cells remains to be poorly understood. We aimed to explore the regulatory mechanism of propofol in hypoxia-injured rat pheochromocytoma (PC-12) cells.MethodsPC-12 cells were exposed to hypoxia, and cell viability and apoptosis were assessed by CCK-8 assay and flow cytometry assay/Western blot analysis, respectively. Effects of propofol on hypoxia-injured cells were measured, and the expression of miR-153 was determined by stem-loop RT-PCR. After that, whether propofol affected PC-12 cells under hypoxia via miR-153 was verified, and the downstream protein of miR-153 as well as the involved signaling cascade was finally explored.ResultsHypoxia-induced decrease of cell viability and increase of apoptosis were attenuated by propofol. Then, we found hypoxia exposure up-regulated miR-153 expression, and the level of miR-153 was further elevated by propofol in hypoxia-injured PC-12 cells. Following experiments showed miR-153 inhibition reversed the effects of propofol on hypoxia-treated PC-12 cells. Afterwards, we found BTG3 expression was negatively regulated by miR-153 expression, and BTG3 overexpression inhibited the mTOR pathway and AMPK activation. Besides, hypoxia inhibited the mTOR pathway and AMPK, and these inhibitory effects could be attenuated by propofol.ConclusionPropofol protected hypoxia-injured PC-12 cells through miR-153-mediataed down-regulation of BTG3. BTG3 could inhibit the mTOR pathway and AMPK activation.

The role of propofol on mouse oocyte meiotic maturation and early embryo development

SummaryPropofol is a intravenous anaesthetic most commonly used in ultrasound oocyte retrieval. We studied if the use of propofol had an effect on mouse oocyte maturation, pregnancy, childbirth and progeny and investigated the correlation between propofol side effects and reproductive performance in mice. There was no statistical difference in mating, pregnancy, childbirth, litter size, the number of stillbirths and survival between each group (P>0.05). Propofol also had no effect on polar body extrusion in oocyte maturation as well as on pronucleus formation and, subsequently, early embryo development (P>0.05). An increased concentration of propofol had no effect on this result, although propofol at more than 0.01 mg/ml reduced polar body extrusion. Different concentrations of propofol had no effect on oocyte culture in vitro, pronucleus formation and early embryo development.

Propofol inhibits Wnt signaling and exerts anticancer activity in glioma cells.

Aberrant activation of Wnt signaling is implicated in gliomagenesis. Propofol, the most commonly used intravenous anesthetic agent in clinics, exhibits potent antitumor activity in a variety of cancer cells through different mechanisms. However, the role of propofol on Wnt signaling and glioma cell growth remains to be fully elucidated. In the present study, propofol was identified as a potent inhibitor of Wnt signaling. In 293T cells transfected with Wnt1 or Wnt3 expression plasmids or treated with Wnt3A-conditioned medium, propofol significantly inhibited the transcriptional activity of the SuperTopFlash reporter and the expression of Wnt target genes. The inhibitory effect of propofol on Wnt signaling was also observed in glioma cells. Further experiments demonstrated that propofol suppressed glioma cell growth by decreasing cell proliferation and enhancing cell apoptosis. Finally, the potential antitumor efficiency of propofol was confirmed using xenograft experiments in vivo. Taken together, the results indicated a novel mechanism for the anticancer activity of propofol and provide supporting evidence for its use as a prospective anticancer drug to treat glioma in patients with deregulated Wnt signaling.

Propofol inhibits proliferation, migration, and invasion but promotes apoptosis by regulation of Sox4 in endometrial cancer cells.

Propofol is an intravenous sedative hypnotic agent of which the growth-inhibitory effect has been reported on various cancers. However, the roles of propofol in endometrial cancer (EC) remain unclear. This study aimed to explore the effects of propofol on EC in vitro and in vivo. Different concentrations of propofol were used to treat Ishikawa cells. Colony number, cell viability, cell cycle, apoptosis, migration, and invasion were analyzed by colony formation, MTT, flow cytometry, and Transwell assays. In addition, the pcDNA3.1-Sox4 and Sox4 siRNA plasmids were transfected into Ishikawa cells to explore the relationship between propofol and Sox4 in EC cell proliferation. Tumor weight in vivo was measured by xenograft tumor model assay. Protein levels of cell cycle-related factors, apoptosis-related factors, matrix metalloproteinases 9 (MMP9), matrix metalloproteinases 2 (MMP2) and Wnt/β-catenin pathway were examined by western blot. Results showed that propofol significantly decreased colony numbers, inhibited cell viability, migration, and invasion but promoted apoptosis in a dose-dependent manner in Ishikawa cells. Moreover, propofol reduced the expression of Sox4 in a dose-dependent manner. Additionally, propofol significantly suppressed the proportions of Ki67+ cells, but Sox4 overexpression reversed the results. Furthermore, in vivo assay results showed that propofol inhibited tumor growth; however, the inhibitory effect was abolished by Sox4 overexpression. Moreover, propofol inhibited Sox4 expression via inactivation of Wnt/β-catenin signal pathway. Our study demonstrated that propofol inhibited cell proliferation, migration, and invasion but promoted apoptosis by regulation of Sox4 in EC cells. These findings might indicate a novel treatment strategy for EC.

Neuroprotection by Propofol Post-Conditioning: Focus on PKMζ/KCC2 Pathway Activity.

Critical and major operations are often accompanied by brain ischemic complications. Previous studies found that propofol post-conditioning provided neuroprotective functions through upregulating the expression of potassium chloride cotransporter 2 (KCC2) in gamma-aminobutyric acid (GABA) interneurons. Membrane expression and phosphorylation represents KCC2 activity, which were modulated by a protein kinase C (PKC)-dependent mechanism. However, the role of propofol in increasing KCC2 phosphorylation and the involvement of protein kinase Mζ (PKMζ), a major subtype of PKC, in the KCC2 pathway remained unclear. In this study, we established middle cerebral artery occlusion model in rats to evaluate the long-term recovery of brain functions using behavioral experiments. KCC2 and PKMζ were assessed via western blot. We used the selective inhibitor, zeta inhibitory peptide (ZIP), to investigate the relationship between KCC2 and PKMζ. Intracellular chloride concentration in the hippocampal CA1 area was measured to determine KCC2 activity. We found that propofol, infused at a speed of 20mgkg-1h-1 for 2h at the onset of reperfusion, improved neurological deficits and cognitive dysfunction following ischemia/reperfusion injury. PKMζ expression was significantly upregulated, which improved KCC2 membrane expression and phosphorylation in the ischemic hippocampal CA1 area, and these effects could last up to 28days. But ZIP inhibited this process. Ultimately, we showed that propofol increased KCC2 phosphorylation and PKMζ was the upstream of KCC2. Propofol led to long-term recovery of brain functions by upregulating the activity of the PKMζ/KCC2 pathway.

The possible role of propofol in drug-induced torsades de pointes: A real-world single-center analysis

BackgroundTorsades de pointes (TdP) is a polymorphic ventricular tachycardia associated with QT prolongation. Propofol is a sedative-anesthetic with proarrhythmic effects on cardiac myocytes. We performed a retrospective study to determine the incidence of TdP following propofol exposure at Mayo Clinic (Rochester, MN) from 08/11/1998–11/20/2015. MethodsWe queried our database using key search terms to identify patients exposed to propofol who developed TdP perioperatively or during non-surgical sedation. QT intervals were obtained from electrocardiograms (ECGs) performed before propofol exposure and after documented TdP and were corrected using Fridericia and Framingham methods. T wave peak-to-end (Tp-e)/QT ratios were also calculated. ResultsA total of 628,784 patients received propofol over 17.3years. Of these patients, 21 developed TdP (12, postoperatively; 3, intraoperatively; 6, during sedation). There were 17 patients who were exposed to at least one factor associated with QT-prolongation, including QT-prolonging medications in 8 patients, heart rate <60 beats per minute in 8 patients, potassium <3.5mmol/L in 4 patients, magnesium <1.8mg/dL in 2 patients, and subarachnoid hemorrhage in 2 patients. The number of patients with QTc>500ms using Fridericia correction was significantly higher from baseline following exposure to propofol (1 patient vs 6 patients, P=0.04); however no significant difference was observed with Framingham correction. ConclusionIn our study, TdP after propofol administration occurred with an annual incidence of 1.93 per million and was often associated with other risk factors. Nevertheless, propofol should be administered with caution in patients at risk of developing TdP.