Effect and mechanism of nuclear receptor Nur77 on oxaliplatin resistance in colon cancer cells

WANG Yingmei; WANG Ying; LI Chao

doi:10.3969/j.issn.1674-4136.2023.06.007

Abstract：Objective To explore the role of nuclear receptor Nur77 in oxaliplatin resistance of colon cancer cells and its related mechanism.Methods Colon cancer cell SW480 was transfected with Nur77 and its inhibitor vector.Normal colon cancer cell SW480 was divided into a blank group and a control group;no-load transfected colon cancer cell SW480 was set as a no-load group;Nur77 vector transfected colon cancer cell SW480 was set as Nur77 overexpression group;and Nur77 inhibitor vector transfected colon cancer cell SW480 was set as Nur77 inhibition group.Colon cancer cells SW480 of each group in logarithmic growth stage were detected by MTT assay under the treatment of 0.5 μg/mL,1.0 μg/mL,2.0 μg/mL,4.0 μg/mL and 8.0 μg/mL olisatin,respectively.The expression levels of NF-κB-p65,IKK,and p-IKK in cells of each group were detected by Western blot.The mRNA expression levels of NF-κB-p65,IKK,and p-IKK in each group were detected by qRT-PCR.Results With the increase of oxalixatin concentration,the survival rate of SW480 decreased gradually,the survival rate of the Nur77 inhibition group was the lowest(P＜0.05),and the survival rate of the Nur77 overexpression group was the highest(P＜0.05).The expression levels of NF-κB-p65,IKK,and P-IKK proteins and their mRNA in colon cancer cells transfected with Nur77 were significantly higher than those in other groups(P＜0.05).The expression levels of NF-κB-p65,IKK,P-IKK protein and mRNA in colon cancer cells transfected with Nur77 inhibitor were significantly decreased compared with those in other groups(P＜0.05).Conclusions With the increase of oxalixatin concentration,the survival rate of colon cancer cells decreased gradually,but the survival rate of colon cancer cells transfected with Nur77 increased abnormally.The high expression of Nur77 could reduce the drug sensitivity of colon cancer cells.Furthermore,the expression levels of NF-κb-p65,IKK,and p-IKK in Nur77 transfected colon cancer cells were also increased.By increasing the expression levels of IKK and p-IKK,improving the activity of the NF-κB signaling pathway may be the main mechanism of reducing the drug sensitivity of colon cancer cells.