|Alternative Title||Effect of Co-SLD on the biological behavior of tongue squamous cell carcinoma and its mechanism|
|Place of Conferral||兰州|
|Keyword||Co-SLD 舌鳞癌细胞 抗肿瘤活性 线粒体功能障碍 斑马鱼胚胎毒性|
|Other Abstract||Objective:The effects of a novel compound containing carbonyl cobalt sulindac derivatives on the biological behavior of tongue squamous cell carcinoma were studied and the underlying mechanism was explored.It provides new ideas possibilities for the prevention and treatment of oral tongue squamous cell carcinoma.|
Methods: 1) In vivo animal experiment:Gradient concentration compound Co-SLD solution (0, DMSO, 5, 10, 20umol / L) was used to treat normal zebrafish embryos 4h (4hpf) after fertilization, and incubated to 144hpf (change culture solution every 24h) ), The hatching rate, mortality, deformity rate, heart rate and swimming distance of larvae were recorded at different time points. Apoptosis of 48 hpf zebrafish was detected by acridine orange (AO) staining.
2) In vitro cell experiments:The oral squamous cell carcinoma cell line CAL27 was treated with gradient concentration Co-SLD (0, DMSO, 5, 10, 20umol/L), and COX-2 content in CAL27 cells treated with Co-SLD was detected by COX-2Elisa kit. Growth curve was used. Cloning assay and Ki67 expression were tested for the effect of Co-SLD on the proliferation of CAL27 cells. The effect of Co-SLD on the migration of CAL27 cells was detected by scratch assay. Flow cytometry was used to detect the apoptosis of CAL27 cells by Co-SLD. The impact of the cycle; and the discussion of relevant mechanisms.
Results:1) Co-SLD Security Assessment:During the early development of zebrafish embryos, Co-SLD did not cause significant toxicity at low concentrations (5 and 10 μM), while zebrafish was significantly toxic at a concentration of 20 uM. The embryo mortality measured at 24hpf increased with the increase of Co-SLD concentration. The embryo mortality rate was about 9.8% at 20μM. The embryo hatching rate was measured at 48hpf. When the Co-SLD concentration was 20uM, the hatching rate decreased to 68.3. %; an increase in the 72hpf deformity rate also demonstrated a significant concentration of high concentration (20 μM) on zebrafish. High concentration (20 μM) of Co-SLD also induced cardiomyocyte apoptosis and heart rate reduction, and inhibited the behavior of zebrafish.
2）Co-SLD efficacy evaluation:2) Evaluation of Co-SLD effectiveness: COX-2 was highly expressed in CAL27 cells. After 24 h of Co-SLD treatment, the expression of COX-2 in tongue squamous carcinoma cells was significantly decreased and inhibited by Co-SLD at 10 μM and 20 μM. Cell proliferation (39.8% reduction compared with the control group), and the cell migration ability was also significantly reduced; apoptosis was concentration-dependent, compared with 0.63% of the control group, the concentration was 10 μM or 20 μM, apoptosis The proportion of cells is as high as 6.96% or 32.8%. As a result of cell cycle experiments, the blockage mainly occurs in the G1 phase, inhibiting DNA synthesis and causing cell proliferation to be blocked. As the concentration of the compound increased, the mitochondrial dysfunction triggered by Co-SLD was characterized by mitochondrial membrane potential destruction. Compared with the control group, the membrane potential of the 10 μM and 20 μM Co-SLD treatment groups decreased by about 26% and 40%. At the same time, the accumulation of high ROS and energy consumption were also concentration-dependent and killed CAL27 cells.
Conclusion:Co-SLD has good anticancer activity against oral squamous cell carcinoma, and the optimal concentration is 10uM, which not only avoids embryonic developmental toxicity, but also enhances the killing of cancer cells by destroying mitochondrial function. In conclusion, Co-SLD is potentially feasible in the treatment of oral tongue squamous cell carcinoma.
|First Author Affilication||School of Stomatology|
|李思睿. Co-SLD对舌鳞癌细胞生物学行为的影响及其机制探讨[D]. 兰州. 兰州大学,2019.|
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