Top

Journal of Experimental & Clinical Cancer Research

Published in:

Open Access 01-12-2012 | Research

Propofol induces proliferation and invasion of gallbladder cancer cells through activation of Nrf2

Authors: Lingmin Zhang, Ning Wang, Suna Zhou, Wenguang Ye, Guixia Jing, Mingxin Zhang

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2012

Abstract

Background

Propofol is one of the most commonly used intravenous anaesthetic agents during cancer resection surgery, but the effect of propofol on gallbladder cancer is not clear. NF-E2-related factor 2 (Nrf2) is abundantly expressed in cancer cells and relates to proliferation, invasion, and chemoresistance. The aims of the current study were to evaluate effects of propofol on the behavior of human GC cells and role of Nrf2 in these effects.

Method

The effects of propofol on cell proliferation, apoptosis, and invasion were detected by MTT assays, flow cytometry, and transwell assay. Also, activation of Nrf2 was determined by western blot, RT-PCR, and immunofluorescence assays. Nrf2 was knocked-down in GBC-SD cells by shRNA before evaluating the role of Nrf2 in the influence of propofol on biological behaviors.

Results

Propofol promoted the proliferation of GBC-SD cells in a dose- and time- dependent manner. After exposure to propofol for 48 h, GBC-SD cells showed decreased apoptosis and increased invasion. Also, propofol over-expressed Nrf2 at both the protein and mRNA levels and induced translocation of Nrf2 into the nucleus. Finally, loss of Nrf2 by shRNA reversed the effect of propofol on cell proliferation, apoptosis, and invasion.

Conclusion

Propofol induces proliferation and promotes invasion of GC cells through activation of Nrf2.

Available only for authorised users

Marik PE: Propofol: therapeutic indications and side-effects. Curr Pharm Des. 2004, 10: 3639-3649. 10.2174/1381612043382846.CrossRefPubMed

Vasileiou I, Xanthos T, Koudouna E, Perrea D, Klonaris C, Katsargyris A, Papadimitriou L: Propofol: a review of its non-anaesthetic effects. Eur J Pharmacol. 2009, 605: 1-8. 10.1016/j.ejphar.2009.01.007.CrossRefPubMed

Wang HH, Zhou HY, Chen CC, Zhang XL, Cheng G: Propofol attenuation of renal ischemia/reperfusion injury involves heme oxygenase-1. Acta Pharmacol Sin. 2007, 28: 1175-1180. 10.1111/j.1745-7254.2007.00566.x.CrossRefPubMed

Xu JJ, Wang YL: Propofol attenuation of hydrogen peroxide-mediated oxidative stress and apoptosis in cultured cardiomyocytes involves haeme oxygenase-1. Eur J Anaesthesiol. 2008, 25: 395-402. 10.1017/S0265021508003542.CrossRefPubMed

Hoetzel A, Schmidt R: Regulatory role of anesthetics on heme oxygenase-1. Curr Drug Targets. 2010, 11: 1495-1503.CrossRefPubMed

Liang C, Xue Z, Wang H, Li P: Propofol upregulates heme oxygenase-1 through activation of ERKs in human umbilical vein endothelial cells under oxidative stress conditions. J Neurosurg Anesthesiol. 2011, 23: 229-235. 10.1097/ANA.0b013e31821c007f.CrossRefPubMed

Jozkowicz A, Was H, Dulak J: Heme oxygenase-1 in tumors: is it a false friend?. Antioxid Redox Signal. 2007, 9: 2099-2117. 10.1089/ars.2007.1659.PubMedCentralCrossRefPubMed

Was H, Dulak J, Jozkowicz A: Heme oxygenase-1 in tumor biology and therapy. Curr Drug Targets. 2010, 11: 1551-1570.CrossRefPubMed

Garib V, Lang K, Niggemann B, Zänker KS, Brandt L, Dittmar T: Propofol-induced calcium signalling and actin reorganization within breast carcinoma cells. Eur J Anaesthesiol. 2005, 22: 609-615. 10.1017/S026502150500102X.CrossRefPubMed

10.

Mammoto T, Mukai M, Mammoto A, Yamanaka Y, Hayashi Y, Mashimo T, Kishi Y, Nakamura H: Intravenous anesthetic, propofol inhibits invasion of cancer cells. Cancer Lett. 2002, 184: 165-170. 10.1016/S0304-3835(02)00210-0.CrossRefPubMed

11.

Miao Y, Zhang Y, Wan H, Chen L, Wang F: GABA-receptor agonist, propofol inhibits invasion of colon carcinoma cells. Biomed Pharmacother. 2010, 64: 583-588. 10.1016/j.biopha.2010.03.006.CrossRefPubMed

12.

Kotani N, Hashimoto H, Sessler DI, Kikuchi A, Suzuki A, Takahashi S, Muraoka M, Matsuki A: Intraoperative modulation of alveolar macrophage function during isoflurane and propofol anesthesia. Anesthesiology. 1998, 89: 1125-1132. 10.1097/00000542-199811000-00012.CrossRefPubMed

13.

Kushida A, Inada T, Shingu K: Enhancement of antitumor immunity after propofol treatment in mice. Immunopharmacol Immunotoxicol. 2007, 29: 477-486. 10.1080/08923970701675085.CrossRefPubMed

14.

Melamed R, Bar-Yosef S, Shakhar G, Shakhar K, Ben-Eliyahu S: Suppression of natural killer cell activity and promotion of tumor metastasis by ketamine, thiopental, and halothane, but not by propofol: mediating mechanisms and prophylactic measures. Anesth Analg. 2003, 97: 1331-1339.CrossRefPubMed

15.

Baird L, Dinkova-Kostova AT: The cytoprotective role of the Keap1-Nrf2 pathway. Arch Toxicol. 2011, 85: 241-272. 10.1007/s00204-011-0674-5.CrossRefPubMed

16.

Surh YJ, Kundu JK, Li MH, Na HK, Cha YN: Role of Nrf2-mediated heme oxygenase-1 upregulation in adaptive survival response to nitrosative stress. Arch Pharm Res. 2009, 32: 1163-1176. 10.1007/s12272-009-1807-8.CrossRefPubMed

17.

Lau A, Villeneuve NF, Sun Z, Wong PK, Zhang DD: Dual roles of Nrf2 in cancer. Pharmacol Res. 2008, 58: 262-270. 10.1016/j.phrs.2008.09.003.PubMedCentralCrossRefPubMed

18.

Wang J, Zhang M, Zhang L, Cai H, Zhou S, Zhang J, Wang Y: Correlation of Nrf2, HO-1, and MRP3 in gallbladder cancer and their relationships to clinicopathological features and survival. J Surg Res. 2010, 164: e99-e105. 10.1016/j.jss.2010.05.058.CrossRefPubMed

19.

Livak KJ, Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)). Method. Methods. 2001, 25: 402-408. 10.1006/meth.2001.1262.CrossRefPubMed

20.

Santamaria LB, Schifilliti D, La Torre D, Fodale V: Drugs of anaesthesia and cancer. Surg Oncol. 2010, 19: 63-81. 10.1016/j.suronc.2009.03.007.CrossRefPubMed

21.

Moi P, Chan K, Asunis I, Cao A, Kan YW: Isolation of NF-E2-related factor 2 (Nrf2), a NF-E2-like basic leucine zipper transcriptional activator that binds to the tandem NF-E2/AP1 repeat of the beta-globin locus control region. Proc Natl Acad Sci USA. 1994, 91: 9926-9930. 10.1073/pnas.91.21.9926.PubMedCentralCrossRefPubMed

22.

Zhang DD: Mechanistic studies of the Nrf2-Keap1 signaling pathway. Drug Metab Rev. 2006, 38: 769-789. 10.1080/03602530600971974.CrossRefPubMed

Title: Propofol induces proliferation and invasion of gallbladder cancer cells through activation of Nrf2
Authors: Lingmin Zhang
Ning Wang
Suna Zhou
Wenguang Ye
Guixia Jing
Mingxin Zhang
Publication date: 01-12-2012
Publisher: BioMed Central
Published in: Journal of Experimental & Clinical Cancer Research / Issue 1/2012
Electronic ISSN: 1756-9966
DOI: https://doi.org/10.1186/1756-9966-31-66

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Method

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 1/2012

Increased expression of CD133 and reduced dystroglycan expression are strong predictors of poor outcome in colon cancer patients

Intracerebral delivery of Carboplatin in combination with either 6 MV Photons or monoenergetic synchrotron X-rays are equally efficacious for treatment of the F98 rat glioma

Interspecies differences in membrane-associated protease activities of thyrocytes and their relevance for thyroid cancer studies

Mechanisms involved in PGE2-induced transactivation of the epidermal growth factor receptor in MH1C1 hepatocarcinoma cells

Oncolytic adenovirus armed with IL-24 Inhibits the growth of breast cancer in vitro and in vivo

Over-expression of BMPR-IB reduces the malignancy of glioblastoma cells by upregulation of p21 and p27Kip1

Keynote webinar | Spotlight on antibody–drug conjugates in cancer