Sevoflurane and Propofol Co-affect the Development of Colorectal Cancer by Regulating TM2D1.

AIMS: Sevoflurane and propofol are the most commonly used anesthetics in surgery. In this study, we aim to explore and clarify the function of sevoflurane and propofol in colorectal cancer. METHODS: Cell counting kit-8, colony formation, western blot, and transwell assays were performed to determine cell proliferation, apoptosis, ferroptosis, invasion, and migration. We performed overexpression experiments to detect the underlying molecular mechanism of sevoflurane and propofol. The genes related to epithelial-mesenchymal transition were measured by western blot. RESULTS: We discovered that sevoflurane and propofol co-treatment exerted more anti-tumor activities than just sevoflurane or propofol treatment in colorectal cancer cells in vitro. Mechanistically, our data showed that sevoflurane and propofol-induced apoptosis and ferroptosis and inhibited cell proliferation, invasion, and migration. Additionally, TM2D1 was considered a target of sevoflurane and propofol, and TM2D1 overexpression reversed the effect of sevoflurane and propofol on colorectal cancer cell biology behaviors. CONCLUSION: Our results showed a novel anti-tumor mechanism of sevoflurane and propofol in colorectal cancer cells, and TM2D1 might be an underlying therapeutic target for treating colorectal cancer patients.

Sufentanil promotes autophagy and improves ischemia-reperfusion-induced acute kidney injury via up-regulating microRNA-145. / 舒芬太尼通过上调microRNA-145促进自噬和改善缺血再灌注诱导的急性肾损伤.

OBJECTIVES: Sufentanil has a good protective effect on myocardial and liver injury caused by ischemia reperfusion (IR), but its protective effect on kidney is still unclear. This study aims to investigate whether sufentanil can prevent IR-induced acute kidney injury (AKI) and to determine whether its efficacy is related to miR-145-mediated autophagy. METHODS: A total of 40 rats were randomly divided into 5 groups (n=8 in each group): A sham group, an IR group, a sufentanil group, a sufentanil+miR-145 inhibitor control group (an anti-NC group) and a sufentanil+miR-145 inhibitor group (an anti-miR-145 group). Except for the sham group, the other groups established a rat AKI model induced by IR. The sufentanil group, the sufentanil+anti-NC group, and the sufentanil+anti-miR-145 were injected with sufentanil (1 µg/kg) through femoral vein 30 min before ischemia. The sufentanil+anti-NC group and the sufentanil+anti-miR-145 group were injected with miR-145 inhibitor control or anti-miR-145 (80 mg/kg) through the tail vein before sufentanil pretreatment. The structure and function of kidneys harvested from the rats were evaluated, and the protein levels of autophagy-related proteins, oxidative stress levels, and apoptosis levels were measured. RESULTS: Compared with the IR group, the renal structure and function were improved in the sufentanil group. The levels of blood urea nitrogen (BUN), creatinine (Cr), urinary kidney injury molecule 1 (KIM-1), neutrophil gelatinase related lipid transporter (NGAL), tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, IL-6 and ROS were significantly decreased (all P<0.05). In addition, compared with the IR group, the levels of Beclin-1 and LC3 in renal tissues in the sufentanil group were significantly increased (both P<0.05), and the apoptosis in renal tissues was significantly reduced (P<0.05). Compared with the sufentanil+anti-NC group, the levels of BUN, Cr, KIM-1, NGAL, TNF-α, IL-1ß, IL-6 and ROS in the sufentanil+anti-miR-145 group were significantly increased (all P<0.05), the levels of Beclin-1 and LC3 in renal tissues were significantly decreased (both P<0.05), and the apoptosis in renal tissues was significantly increased (P<0.05). CONCLUSIONS: Sufentanil can prevent the AKI induced by IR, which is related to the up-regulation of miR-145-mediated autophagy.

Oxymatrine inhibits proliferation and apoptosis of human breast cancer cells through the regulation of miRNA-140-5P.

OBJECTIVE: Oxymatrine has shown strong anti-cancer ability, but its mechanism is not well-studied. METHODS: The inhibitory rates of oxymatrine with various concentrations (0, 1, 2, 4, 6, 8, 16, 32 mg/ml) on MCF-7 cells were detected by CCK-8. The effects of oxymatrine on the expression of miRNA-140-5P in MCF-7 cells were detected by real-time fluorescent quantitative PCR (RT-PCR). miRNA-140-5P mimics or NC mimics were transfected into cells using Lipofectamine 2000. Eventually, the cells were divided into control-group, drug-group, miRNA-140-5P mimics group, NC mimics group, and miRNA-140-5P mimics + drug group. Cell viability was detected by CCK-8 assay and apoptosis rate of each group were measured by using Flow cytometry. Western blot was carried out to detect the protein expression of TGFBR1 and FGF9. RESULTS: Oxymatrine at various concentrations had conspicuous inhibitory effect on the proliferation of MCF-7 cells (P<0.05), and the inhibitory effect of oxymatrine on MCF-7 cells showed both dose- and time-dependent manners. The relative expression of miRNA-140-5P in MCF cells was remarkably lower than that in MCF-10A. Oxymatrine could effectively promote the expression of miRNA-140-5P in MCF-7 cells, and the relative expression of miRNA-140-5P increased significantly with the increased dose of oxymatrine (P<0.05). Both transfection of miRNA-140-5P mimics and oxymatrine treatment could reduce the proliferation of MCF-7 cells (P<0.05), and the proliferation of cells in miRNA-140-5P mimics + drug-group was significantly lower than that of other groups (P<0.05). Compared with the control-group, the protein expressions of TGFbR1 and FGF9 in low-dose, medium-dose and high-dose groups were dramatically decreased (P<0.05), in a dose-dependent manner (P<0.05). CONCLUSION: Oxymatrine inhibits proliferation and promotes cell apoptosis of breast cancer MCF-7 cells. The mechanism may contribute to the regulation of miRNA-140-5p and its target genes.