目的：探讨七氟烷（sevoflurane）通过调控PI3K磷酸化对结肠癌SW480 细胞增殖和侵袭以及裸鼠移植瘤生长的影响及其机制。方法：采用七氟烷处理结肠癌SW480 细胞，将细胞随机分为对照组、0.5%七氟烷组、1.0%七氟烷组和2.0%七氟烷组进行后续实验。用克隆形成实验检测SW480 细胞的增殖能力，RT-PCR 检测细胞中MDM2、survivin mRNA表达水平，Transwell小室法检测细胞的侵袭能力，Western blotting 检测细胞中MDM2、survivin、VEGF、PI3K、p-PI3K、AKT、p-AKT 蛋白的表达水平。并加入PI3K激活剂740 Y-P 进行验证。建立裸鼠SW480 细胞移植瘤模型，称取肿瘤质量，免疫组化检测移植瘤组织中MDM2 和VEGF阳性表达率。结果：与对照组和低剂量组比较，1.0%和2.0%七氟烷组SW480 细胞的克隆形成率显著降低（均P<0.01）；细胞中MDM2 mRNA和蛋白水平显著升高（均P<0.01），survivin mRNA和蛋白水平显著降低（均P<0.01）；SW480 细胞侵袭数显著降低（P<0.01），VEGF、p-PI3K/PI3K、p-AKT/AKT 蛋白水平显著降低（均P<0.01）。740Y-P 可逆转七氟烷对SW480 细胞增殖、侵袭及PI3K/AKT信号通路相关蛋白表达的影响。2.0%七氟烷组小鼠移植瘤质量显著降低（P<0.01），瘤组织中MDM2 阳性表达率显著升高（P<0.01）、VEGF阳性表达率显著降低（P<0.01）。结论：七氟烷抑制结肠癌SW480 细胞的增殖和侵袭以及裸鼠移植瘤的生长，其作用机制可能是通过抑制PI3K磷酸化实现的。

Objective: To investigate the effect and mechanism of sevoflurane on the proliferation and invasion of colon cancer SW480 cells and the growth of transplanted tumor in nude mice by regulating the phosphorylation of PI3K. Methods: Colon cancer SW480 cells were treated with sevoflurane and randomly divided into control group, 0.5% sevoflurane group, 1.0% sevoflurane group and 2.0% sevoflurane group for subsequent experiments. The proliferation ability of SW480 cells was detected by Clone formation assay, mRNA expression levels of MDM2 and survivin in cells were detected by RT-PCR, invasion ability of cells was detected by Transwell assay, and protein expression levels of MDM2, survivin, VEGF, PI3K, p-PI3K, AKT and p-AKT were detected by Western blotting. PI3K activator 740Y-P was added for verification. SW480 cell transplanted tumor model was constructed on nude mice, and the tumor mass was weighed. The positive expression rates of MDM2 and VEGF in the transplanted tumor tissues were detected by Immunohistochemistry. Results: As compared with the control group and the low-dose group, the clone formation rate of SW480 cells and the number of invaded cells in the 1.0% and 2.0% sevoflurane groups were significantly decreased (all P<0.01), the mRNA and protein levels of MDM2 in the cells were significantly increased (all P<0.01), while the mRNA and protein levels of survivin were significantly decreased (all P<0.01); and the protein levels of VEGF, p-PI3K/PI3K and p-AKT/AKT were significantly decreased (all P<0.01). 740Y-P could reverse the effect of sevoflurane on the proliferation, invasion and expression of proteins associated with the PI3K/AKT signaling pathway in SW480 cells. The mass of transplanted tumor in 2.0% sevoflurane group was significantly decreased (P<0.01), and the positive MDM2 expression rate in tumor tissues was significantly increased (P<0.01), while the positive VEGF expression rate was significantly decreased (P<0.01). Conclusion: Sevoflurane inhibits the proliferation and invasion of colon cancer SW480 cells and the growth of xenografts in nude mice possibly by inhibiting PI3K phosphorylation.

黑龙江省自然科学基金资助项目（No. H2017016）