Effects of Sevoflurane on Lewis Lung Carcinoma Cell Proliferation In Vivo and In Vitro

Abstract

Background and objectives: There are several studies that sevoflurane could enhance proliferation of cancer cells, while others suggest no effect on clinical outcome. We conducted in vivo and in vitro experiments to investigate the effects of sevoflurane, a volatile anesthetic, on proliferation and outcomes of Lewis lung carcinoma (LLC) cells. Materials and Methods: A total of 37 mice were injected with LLC cells to compare the tumor size and survival of the sevoflurane exposed group (sevo group) and control group. The sevo group was exposed to 2% sevoflurane and 4 L/min of oxygen for 1 h per day 3 times per week, and the control group was exposed only to 4 L/min of oxygen. In vitro study, 12 plates incubated with LCC cells. 6 plates were exposed to 2% sevoflurane for 1 hr/day for 3 days and 6 plates were not exposed, and cell proliferation was compared after 3 days. Results: There were no significant differences in survival or tumor size between mice exposed to sevoflurane and control mice (survival: 29.06 ± 4.45 vs. 28.76 ± 3.75, p = 0.836; tumor size: 0.75 (0.41–1.02) vs. 0.49 (0.11–0.79), p = 0.153). However, in vitro study, the proliferation of LLC cells exposed to sevoflurane increased by 9.2% compared to the control group (p = 0.018). Conclusions: Sevoflurane (2 vol%) exposure could promote proliferation of LLC cells in vitro environment, but may not affect proliferation of LLC cells in vivo environment. These results suggest that in vitro studies on the effects of anesthetics on cancer may differ from those of in vivo or clinical studies.

Application of Anesthetics in Cancer Patients: Reviewing Current Existing Link With Tumor Recurrence

“…Volatile anesthetics not only cause immune cell dysfunction but apoptosis of neutrophils and T-lymphocytes ( 38 , 39 ), as sevoflurane, one of the most commonly used inhalation anesthetics, induces apoptosis and oxidative stress in lymphocytes ( 40 ). In another study, although there were no significant differences in tumor size or survival between sevoflurane and control mice, in vitro study showed that the proliferation of Lewis lung carcinoma cells exposed to sevoflurane increased by 9.2% compared to the controls ( 41 ). This implies that sevoflurane exposure might enhance the proliferation of tumor cells in vitro environment, but might not affect proliferation in vivo , suggesting that the effects of anesthetics on in vitro studies of cancer do not necessarily translate into in vivo or clinical studies.…”

Effect of Sevoflurane on the Proliferation of A549 Lung Cancer Cells

“…During the experimental period, the tumor size and mouse weight were measured. The length and width of the tumor were measured by a caliper and the tumor volume was calculated as follows [ 14 , 15 ]: tumor volume (cm 3 ) = length × width 2 × 0.5 …”

“…Some studies suggest a possible link between sevoflurane exposure and increased risk of cancer recurrence and mortality in patients undergoing cancer surgery [ 6 , 7 ]. Other studies have not found any significant association [ 14 ]. It is important to note that cancer development is a complex process that involves many factors, including genetic predisposition, lifestyle, environmental exposure, and other medical conditions.…”

Effect of total intravenous versus inhalation anesthesia on long-term oncological outcomes in patients undergoing curative resection for early-stage non-small cell lung cancer: a retrospective cohort study

“…Isoflurane activates the Akt-mTOR signaling pathway; further, it promotes proliferation, migration, and invasiveness of NSCLC cells, resulting in pro-tumor effects [15]. Exposure of Lewis lung carcinoma cells to sevoflurane promotes cell proliferation in vitro [28]. However, another in vitro study reported that sevoflurane exerts antitumor effects by inhibiting the proliferation and invasion of lung adenocarcinoma cells and enhancing apoptosis by regulating the long chain RNA PCAT6/miR-326/Wnt5a/β-catenin axis [29].…”