Effect of Sevoflurane on the Proliferation of A549 Lung Cancer Cells

Abstract

Background and Objectives: Sevoflurane has opposing effects on cancer progression, depending on its concentration and the cancer type. This study investigated the effects of sevoflurane on the proliferation of A549 lung cancer cells. Materials and Methods: In vitro, the number of A549 cells exposed to different concentrations of sevoflurane was counted. The size and weight of tumors from a xenograft mouse model exposed to air or sevoflurane were measured in vivo experiments. Additionally, hematoxylin and eosin staining and immunohistochemical detection of Ki-67 in the harvested tumor tissues were performed. Results: A total of 72 culture dishes were used and 24 dishes were assigned to each group: Air group; 2% Sevo group (air + 2% sevoflurane); and 4% Sevo group (air + 4% sevoflurane). The number of A549 cells in the 2% Sevo group was less than that in the Air and 4% Sevo groups (Air: 7.9 ± 0.5; 0.5, 2% Sevo: 6.8 ± 0.4, 4% Sevo: 8.1 ± 0.3; p = 0.000). The tumor size was not significantly different between the two groups (Air: 1.5 ± 0.7, 2% Sevo: 2.4 ± 1.9; p = 0.380). Conclusions: The in vitro data showed that sevoflurane inhibited the proliferation of A549 lung cancer cells in a concentration-specific manner. However, the in vivo data showed no correlation between sevoflurane exposure and A549 cell proliferation. Thus, further research is required to understand fully the effects of sevoflurane on cancer progression and to reconcile differences between the in vitro and in vivo experimental results.

Keywords: A549 cells; lung cancer; sevoflurane.

Figure 1

Schematic illustration for the in vitro study with oxygen.

Figure 2

Schematic illustration for the in vitro study with air.

Figure 3

Schematic illustration for the in vivo study with air.

Figure 4

A549 cancer cell proliferation after sevoflurane exposure in vitro studies. (a) Representative microscopic images when A549 cells were exposed to 0%, 2%, or 4% sevoflurane with oxygen or (b) with air for three days (×40). (c) A comparative analysis of the number of A549 cells exposed to the different concentration of sevoflurane with oxygen (left figure, total n = 36) or air (right figure, total n = 72) on day 4. Data are presented as the mean ± SD. * represents p < 0.01, compared with 0% sevoflurane.

Figure 4

A549 cancer cell proliferation after sevoflurane exposure in vitro studies. (a) Representative microscopic images when A549 cells were exposed to 0%, 2%, or 4% sevoflurane with oxygen or (b) with air for three days (×40). (c) A comparative analysis of the number of A549 cells exposed to the different concentration of sevoflurane with oxygen (left figure, total n = 36) or air (right figure, total n = 72) on day 4. Data are presented as the mean ± SD. * represents p < 0.01, compared with 0% sevoflurane.

Figure 5

Comparison of the harvested tumor size in Air group and 2% Sevo group.

Figure 6

Pathological analysis of resected tumor tissues. (a) Representative example of H&E staining of A549 tumor tissues with necrosis (×100). Yellow arrows indicate necrosis area with inflammation. (b) Representative example of Ki-67 immunohistochemistry (×400). Tumor cells with brown colored nucleus were counted as positive.