Isoflurane Promotes Non-Small Cell Lung Cancer Malignancy by Activating the Akt-Mammalian Target of Rapamycin (mTOR) Signaling Pathway

Abstract

BackgroundLung cancer is one of the leading causes of cancer mortalities worldwide, and non-small cell lung cancer (NSCLC) accounts for the majority of all lung cancer cases. Surgery remains one of the front-line treatment options for NSCLC, but events within the perioperative period were found to affect cancer prognosis, such as anesthesia procedures. Isoflurane, a commonly used volatile anesthetic, enhances the malignant potential of renal, prostate, and ovarian cancer cells, but its effects on NSCLC development have not been previously reported.Material/MethodsCCK-8 and MTT cell proliferation assays were used to analyze NSCLC cell proliferation. Metastatic ability was examined by wound healing and transwell assays. We used Western blot analysis to study the mechanism of effect of Isoflurane in NSCLC development.ResultsWe demonstrated that isoflurane promotes proliferation, migration and invasiveness of NSCLC cells, as well as upregulation of the Akt-mTOR signaling pathway in NSCLC cells. Pharmacological inhibition of Akt-mTOR signaling abolished the ability of isoflurane to promote proliferation, migration, and invasion of NSCLC cells, indicating that isoflurane promotes NSCLC cell malignancy by activating the Akt-mTOR signaling pathway.ConclusionsIsoflurane promotes NSCLC proliferation, migration and invasion by activating the Akt-mTOR signaling pathway.

Overcoming resistance to mitochondrial apoptosis by BZML‐induced mitotic catastrophe is enhanced by inhibition of autophagy in A549/Taxol cells

“…The acquired resistance in cancer cells is often associated with more malignancy, which is reflected by rapid proliferation of cancer cells and poor efficacy of anti‐cancer drugs . In our study, the therapeutic dose of Taxol used in A549 cell‐bearing mice failed to inhibit tumour growth in A549/Taxol cell‐bearing mice.…”

<p>The Role of Inhaled Anesthetics in Tumorigenesis and Tumor Immunity</p>

“…47 Moreover, isoflurane increased NSCLC cell migration and invasion by activating the Akt-mTOR signaling pathway. 48 In line with these, isoflurane enhanced cancer cell migration through upregulating the expression of HIF-1α and its downstream genes in prostate cancer 42 (Table 2, Figure 3).…”

“…Due to its low solubility, desflurane can be eliminated more quickly and consequently be awaken more easily. 49 For colon cancer surgery, patients treated with desflurane anesthesia were associated with a higher mortality rate (43.5% versus 13.4%), a higher local recurrence (9.1% [42,44] Activates Akt-mTOR pathway Promotes NSCLC cells proliferation, migration and invasion [48] Upregulates Caveolin-1 Induces colon cancer cell apoptosis [45] Upregulates MMP-2 and MMP-9,…”

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“…In addition, the observation in our patient of a prompt and stable response to rapamycin treatment clearly suggested a key role for mTOR in the pathogenesis of the disease and further supported the hypothesis of a neoplastic nature of BMPM. Indeed, the PI3K/Akt/mTOR pathway has been shown to play a role in the development and progression of several neoplastic diseases [ 17 – 19 ]. mTOR sits at an intersection of several inputs to the cell, integrating signals from both growth factors and nutrients and mediating its effects through two main effectors, p70S6 kinase and 4E-BP1/eIF4E, with a well-defined role in the regulation of protein translation [ 17 , 18 , 20 ].…”