Oxycodone Hydrochloride Inhibits the Malignant Biological Behavior of Rectal Cancer Cells through the AKT/GSK3β/EMT Axis
WANG Yiyun, TIAN Xia*
This study investigates whether OXY (oxycodone hydrochloride) can inhibit the malignant bio logical behavior of rectal cancer cells by regulating the AKT/GSK3β/EMT axis. Rectal cancer cells SW1463 were assigned into Control group, SC79 group (8 μg/mL SC79), OXY-L group (5 mmol/L OXY), OXY-H group (10 mmol/L OXY), and OXY-H+SC79 (AKT activator) group (10 mmol/L OXY and 8 μg/mL SC79). MTT as say and Edu staining were applied to detect cell proliferation. The cell scratch assay was applied to detect cell migration. Transwell method was applied to detect cell invasion. Flow cytometry was used to detect cell apoptosis. ELISA was used to detected the content of CXCL-2 and CXCL-8 in cell supernatant. Western blot was used to detect the expression levels of related proteins. A nude mouse tumor transplantation model was established to observe the effect of OXY on the growth of the transplanted tumors. SC79 could increase D490 (24 h, 48 h) value, proliferation rate, scratch healing rate, invasion number, CXCL-2 content, CXCL-8 content, and the expression levels of PCNA, MMP-9, p-AKT/AKT, p-GSK3β/GSK3, N-cadherin and vimentin in SW1463 cells; while the apoptosis rate, cleaved caspase-3 and E-cadherin expression levels were decreased (P<0.05). OXY decreased D490 (24h, 48h) values, proliferation rate, scratch healing rate, invasion number, CXCL-2 content, CXCL-8 content, and the expres sion levels of PCNA, MMP-9, p-AKT/AKT, p-GSK3β/GSK3, N-cadherin and vimentin in SW1463 cells, while in creased apoptosis rate, cleaved caspase-3 and E-cadherin protein expression levels (P<0.05). SC79 could reduce the inhibitory effect of OXY on the malignant biology of rectal cancer cells (P<0.05). OXY could inhibit the growth of tumors, reduce tumor mass and volume, and increase the apoptosis rate of tumor cells in nude mice, meanwhile it could decrease the expression levels of p-AKT/AKT, p-GSK3β/GSK3β, N-cadherin and vimentin proteins in tumor tissues, and increase the expression level of E-cadherin protein and the apoptosis rate (P<0.05). OXY could inhibit the malignant biological behaviors of rectal cancer cells by suppressing the AKT/GSK3β/EMT axis.
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