The synergistic mechanisms of propofol with cisplatin or doxorubicin in human ovarian cancer cells.

Publisher: BioMed Central Country of Publication: England NLM ID: 101474849 Publication Model: Electronic Cited Medium: Internet ISSN: 1757-2215 (Electronic) Linking ISSN: 17572215 NLM ISO Abbreviation: J Ovarian Res Subsets: MEDLINE

Original Publication: [London] : BioMed Central, c2008-

Propofol*/pharmacology ; Propofol*/therapeutic use ; Cisplatin*/pharmacology ; Cisplatin*/therapeutic use ; Doxorubicin*/pharmacology ; Doxorubicin*/therapeutic use ; Ovarian Neoplasms*/drug therapy ; Ovarian Neoplasms*/pathology ; Drug Synergism* ; Apoptosis*/drug effects; Humans ; Female ; Cell Line, Tumor ; Membrane Potential, Mitochondrial/drug effects ; Autophagy/drug effects ; Antineoplastic Agents/pharmacology ; Antineoplastic Agents/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/pharmacology ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use

Background: Most ovarian cancer cases are diagnosed at an advanced stage, leading to poor outcomes and a relatively low 5-year survival rate. While tumor resection in the early stages can be highly effective, recurrence following primary treatment remains a significant cause of mortality. Propofol is a commonly used intravenous anesthetic agent in cancer resection surgery. Previous research has shown that propofol anesthesia was associated with improved survival in patients undergoing elective surgery for epithelial ovarian cancer. However, the underlying antitumor mechanisms are not yet fully understood.
Methods: This study aimed to uncover the antitumor properties of propofol alone and combined with cisplatin or doxorubicin, in human SKOV3 and OVCAR3 ovarian cancer cells. We applied flowcytometry analysis for mitochondrial membrane potential, apoptosis, and autophagy, colony formation, migration, and western blotting analysis.
Results: Given that chemotherapy is a primary clinical approach for managing advanced and recurrent ovarian cancer, it is essential to address the limitations of current chemotherapy, particularly in the use of cisplatin and doxorubicin, which are often constrained by their side effects and the development of resistance. First of all, propofol acted synergistically with cisplatin and doxorubicin in SKOV3 cells. Moreover, our data further showed that propofol suppressed colony formation, disrupted mitochondrial membrane potential, and induced apoptosis and autophagy in SKOV3 and OVCAR3 cells. Finally, the effects of combined propofol with cisplatin or doxorubicin on mitochondrial membrane potential, apoptosis, autophagy, and epithelial-mesenchymal transition were different in SKOV3 and OVCAR3 cells, depending on the p53 status.
Conclusion: In summary, repurposing propofol could provide novel insights into the existing chemotherapy strategies for ovarian cancer. It holds promise for overcoming resistance to cisplatin or doxorubicin and may potentially reduce the required chemotherapy dosages and associated side effects, thus improving treatment outcomes.
(© 2024. The Author(s).)

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A1111035 to S-M Huang Teh-Tzer Study Group for Human Medical Research Foundation; NSTC 112-2635-B016-002 to J-L Chen National Science and Technology Council; KMUHIRB-F(II)-20220157 to Z-F Wu Kaohsiung Medical University Hospital

Keywords: Cisplatin; Combinatory therapy; Doxorubicin; Ovarian cancer; Propofol

YI7VU623SF (Propofol)
Q20Q21Q62J (Cisplatin)
80168379AG (Doxorubicin)
0 (Antineoplastic Agents)

Date Created: 20240913 Date Completed: 20240914 Latest Revision: 20240916

20240916

PMC11401282

10.1186/s13048-024-01509-x

39272193