Review
Effects of propofol on cancer development and chemotherapy: Potential mechanisms

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Abstract

Propofol (2, 6-diisopropylphenol) is the commonly used intravenous sedative-hypnotic agent. Accumulating evidence shows that propofol affects cancer development by direct and indirect ways. In this review, we will provide an overview of the effects of propofol on cancer development and chemotherapy, with a special focus on the underlying molecular mechanisms involved. Propofol regulates both microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), and serves as a regulator of different signaling pathways including hypoxia-inducible factor-1α (HIF-1α), mitogen-activated protein kinase (MAPK), nuclear factor-kappaB (NF-κB), and nuclear factor E2-related factor-2 (Nrf2) pathways. In addition, propofol modulates host immune function. Possible correlation between propofol and cancer should be verified in further studies, including animal trials and prospective clinical studies.

Introduction

The occurrence of cancer is increasing because of the growth and aging of the population, as well as an increasing prevalence of established risk factors (Torre et al., 2015). Despite significant advances in oncological therapies, cancer remains a major cause of morbidity and mortality. Surgical resection is the principal treatment method for most solid tumors. However, the guideline of anesthesia procedures for cancer patients is limited (Kurosawa, 2012). Growing evidence points that anesthetics influence longer-term outcome of patients after surgery, particularly cancer recurrences (Bajwa et al., 2015, Cassinello et al., 2015, Snyder and Greenberg, 2010). In order to choose the optimal anesthetics and achieve adequate anesthesia management for cancer patients, it is necessary to get a better understanding of how anesthetics affect the long-term outcome of cancer patients.(Fig. 1)

Propofol (2, 6-diisopropylphenol), one of the commonly used intravenous sedative-hypnotic agent with characteristics of smooth induction and rapid recovery from anesthesia, is extensively used for cancer resection surgery. Apart from its multiple anesthetic advantages, propofol exerts a number of non-anesthetic effects, including antitumor activity (Kushida et al., 2007, Melamed et al., 2003, Song et al., 2014, Vasileiou et al., 2009). A number of studies have indicated that propofol suppresses the malignancy of a variety of human cancers, such as hepatocellular carcinoma (HCC) (Ou et al., 2017), breast cancer (Ecimovic et al., 2014), lung cancer (Cui et al., 2014), and pancreatic cancer (Wang et al., 2015). Moreover, some studies have suggested a possible correlation between propofol and chemotherapy, though the results are undefined (Li et al., 2017, Zhang et al., 2016).

Propofol has a significant impact on process of cancer spread and chemotherapy, however, the molecular mechanisms underlying these phenomena are complex. Propofol regulates the potential malignant of cancer in direct and indirect ways. On the one hand, propofol affects key RNAs and signaling pathways directly and contributes to development of cancer. On the other hand, propofol modulates host immune function and impacts degree of immunosuppression. Therefore, this review will discuss the effect of propofol on cancer progression, including regulation of microRNAs (miRNAs), long non-coding RNAs (lncRNAs), signaling pathways and immunity system. We also focus on the effect of propofol on chemotherapy.

Section snippets

Propofol and miRNAs

MiRNAs are a class of endogenous, single-stranded, small, non-coding RNAs that negatively regulate gene expression at the post-transcriptional level by mainly binding to 3′-untranslated region (UTR) of target mRNAs (Bartel, 2009). The role for dysregulation of miRNAs in cancer progression has been well established (Bojmar et al., 2013, Dang et al., 2017, MacDonagh et al., 2015). Propofol exerts anti-tumor potential partly due to regulating expression and transfer of miRNAs.

Indirect effect of propofol on cancer development

In addition to the effect on key moleculars and signaling pathways directly, there must be other mechanisms by which propofol contributes to cancer progression.

The cellular immune system is the critical host defence against the cancer development. Studies have shown that propofol modulated host immune function, for instance, by affecting activity of immune cells and cytokines. Propofol promotes the activity of cytotoxic T cells in mice (Kushida et al., 2007) and humans (Ren et al., 2010). In a

Effect of propofol on chemotherapy activity in vitro

Drug resistance is thought to be a major reason for the limited benefit of most cancer therapies (Hughes and Andersson, 2015, Wilting and Dannenberg, 2012). In addition to cancer development, propofol affects chemotherapeutic activity.

Conclusions

Propofol is a widely used intravenous anesthetic. In addition to its sedation/hypnotic properties, there is a casual link between propofol and cancer. However, the possible correlation between propofol and cancer is undefined. Some studies reveal that clinically relevant concentrations of propofol decreases cancer cell malignant and chemoresistance by several signaling pathways. Interestingly, opposite results indicates that propofol promotes the invasion and chemoresistance of different types

Conflicts of interest

None.

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