Effect of Propofol and Sevoflurane Anesthesia on HSP70 Expression in Tumor Cells

Effect of Propofol and Sevoflurane Anesthesia on HSP70 Expression in Tumor Cells A Prospective, Single-center, Pilot, Randomized Study

The goal of this clinical trial is to learn if sevoflurane-based inhalational anesthesia (s-IA) and propofol-based total intravenous anesthesia (p-TVA) have different effects on HSP70 expression in different types of tumour cells. The main questions it aims to answer are:

• if p-TVA/s-IA increase or suppress HSP70 expression in tumor cells in comparison with a pre-anesthesia level;
• does this change in HSP70 expression cause any difference in vital characteristics of tumor cells, such as proliferation, apoptosis, colony formation and migration.

Researchers will compare p-TVA with s-IA by ability of these types of anesthesia to change the HSP70 expression level and modulate HSP70-mediated effects in tumor cells.

Participants will:

• be randomly allocated to p-TVA or s-IA groups;
• donate 12 ml of blood before anesthesia induction and 12 ml after 2 hours of anesthesia.

The blood serum will be used to prepare cell medium. After exposure to this medium, cells from different tumor types will be investigated using cytological and molecular biological methods.

Study Overview

• Status: Active, not recruiting
• Conditions: Cancer; Anesthesia; Cancer Recurrence
• Intervention / Treatment: Drug: Propofol; Drug: Sevoflurane

Detailed Description

This study will be conducted in adult cancer patients who undergo planned radical or palliative tumor resection and signed informed consent. Patients with diabetes mellitus, HIV, hepatitis B and C, as well as patients who undergo emergency surgery will not be included to the study. Patients will be randomly allocated to propofol-based TVA (p-TVA) and sevoflurane-based IA (s-IA) groups. After the collection of blood before the anesthesia induction and in 2 hours of anesthesia, probes will be centrifuged to prepare serum. Cell medium will contain 50% of blood serum. Different tumor cell lines (human lung adenocarcinoma A549, large cell lung carcinoma NCI-H460, human colorectal adenocarcinoma DLD1) will be exposed to the cell medium for 4 hours what corresponds to an approximate duration of anesthesia for oncology surgery. HSP70 expression level will be determined using SDS-PAGE (polyacrilamide gel electrophoresis) and Western-blot analysis (intracellular HSP70 content), ELISA of cell medium (extracellular HSP70 expression) and confocal microscopy.

The A549 cell line with stable knockdown of HSP70 developed by shRNA will be used to distinguish HSP70-based effects of cell medium from p-TVA and s-IA groups on vital characteristics of tumor cells, including proliferation (MTT assay), apoptosis (LDH cytotoxicity assay), colony formation and migration (the Wound healing assay).

Researchers will compare HSP70 expression levels and vital characteristics of tumor cells exposed to patient serum before and after each type of anesthesia, as well as p-TVA group with s-IA group.

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• Russian Federation
  • Saint Petersburg, Russian Federation, 1999034
    • Saint Petersburg State University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosed malignant neoplasm
• Planned surgery for radical or palliative tumor resection
• Age over 18 years
• Signed informed consent

Exclusion Criteria:

• Diabetes mellitus type 2
• HIV, hepatitis B or C
• Emergency surgery
• Known or suspected allergy to studied drugs
• Other conditions when one of the types of anesthesia is more preferable (hemodynamic disorders, bronchial asthma etc)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Propofol-based total venous anesthesia group; These patients will receive total venous anethesia where propofol is used as a hypnotic drug.	Drug: Propofol; Propofol as a part of total venous anesthesia
Experimental: Sevoflurane-based inhalational anesthesia group; These patients will receive inhalational anethesia where sevoflurane is used as a hypnotic drug.	Drug: Sevoflurane; Sevoflurane as a part of intravenous anesthesia

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HSP70 expression in tumor cells in vitro	Increased intracellular and extracellular HSP70 content in different types of tumor cells measured by SDS-PAGE/Western blotting and ELISA, respectively.	24 hours after exposition with patients serum.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
LDG cytotoxicity	Reduction of apoptosis mediated by HSP70 pathway in different types of tumor cells measured by LDG cytotoxicity assay using HSP70-knockdown cell line.	24 hours after exposition with patients serum.
MTT test	Increase in proliferation mediated by HSP70 pathway in different types of tumor cells measured by MTT assay using HSP70-knockdown cell line.	24 hours after exposition with patients serum.
Wound healing test	Increase in cell migration mediated by HSP70 pathway in different types of tumor cells measured by the Wound healing assay.	72 hours after exposition with patients serum.
Cell colonies formation	Increase in ability to form colonies mediated by HSP70 pathway in different types of tumor cells evaluated by direct microscopy using HSP70-knockdown cell line.	7 days after exposition with patients serum.

Collaborators and Investigators

• Sponsor: Saint Petersburg State University, Russia
• Collaborators: Institute of Cytology of the Russian Academy of Sciences; The Russian Science Foundation

Study record dates

Study Major Dates

• Study Start (Actual): October 10, 2024
• Primary Completion (Estimated): November 30, 2025
• Study Completion (Estimated): December 30, 2025

Study Registration Dates

• First Submitted: October 2, 2024
• First Submitted That Met QC Criteria: October 2, 2024
• First Posted (Actual): October 4, 2024

Study Record Updates

• Last Update Posted (Actual): May 4, 2025
• Last Update Submitted That Met QC Criteria: April 30, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: Cancer; Propofol; Anesthesia; Sevoflurane
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Recurrence; Physiological Effects of Drugs; Anesthetics; Central Nervous System Depressants; Platelet Aggregation Inhibitors; Hypnotics and Sedatives; Anesthetics, Intravenous; Anesthetics, General; Anesthetics, Inhalation; Sevoflurane; Propofol
• Other Study ID Numbers: 23-25-00078

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Time Frame: 01/10/2024 - 01/04/2025
• IPD Sharing Access Criteria: By reasonable request.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No