Inhibitory effect of MKK6(E)fusion protein on the growth of ovarian cancer graft tumors in nude mice by regulating the p38/ATF-2 pathway
10.3969/j.issn.1673-4130.2025.11.005
- VernacularTitle:MKK6(E)融合蛋白通过调控p38/ATF-2通路对裸鼠卵巢癌移植瘤生长的抑制作用研究
- Author:
Jin YUAN
1
;
Jiali KANG
;
Xiaoxia WANG
Author Information
1. 广州市第一人民医院/华南理工大学附属第二医院妇产科,广东 广州 510180
- Keywords:
MKK6(E)fusion protein;
ovarian cancer transplantation tumor;
p38/ATF-2 signaling pathway
- From:
International Journal of Laboratory Medicine
2025;46(11):1302-1308
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the inhibitory effect of MKK6(E)fusion protein on the growth of o-varian cancer graft tumors in nude mice and its possible mechanism.Methods A subcutaneous transplantation tumor model in nude mice was constructed using subcutaneous injection of human ovarian cancer HO8910PM cells,which were divided into model group,paclitaxel(positive control,3 mg/mL)group,MKK6(E)fusion protein(1.2 mmol/L)group and MKK6(E)fusion protein+SB202190(p38 agonist,10 μmol/L)group by numerical randomization table,each with 6 animals.The drug was administered continuously in the tail vein for 21 d,once every 3 d.At the end of the administration,the tumor was exfoliated and the tumor volume,mass and tumor inhibition rate were calculated.Serum carbohydrate antigen(CA)125 level was detected by enzyme linked immunosorbent assay(ELISA),histopathology of the tumor was detected by HE staining,and apoptosis of the tumor cells was detected by TUNEL staining.In addition,expression of Fibronectin,matrix metallo-peptidase(MMP)2,and MMP9 were detected by immunohistochemistry,apoptosis and the p38/ATF-2 pathway-related proteins were detected by Western blot.Results Compared with the model group,the tumor volume,mass and serum CA125 level of nude mice in the paclitaxel group and the MKK6(E)fusion protein group were reduced,the tumor suppression rate and the apoptosis rate of cancer cells were increased,the volume of cancer cells in the transplanted tumor tissue was reduced,the nucleus was lightly stained,the di-viding heterogeneity was reduced compared with that of the model group,and the large area of lamellar nec-rotic zone and apoptotic cells were seen,and the expression of Fibronectin,MMP2 and MMP9 was reduced.Bax and Cleaved caspase 3 expression was up-regulated,and Bcl-2 expression and phosphorylated p38(p-p38)/p38 and p-ATF-2/ATF-2 were down-regulated(P＜0.05).Compared with the MKK6(E)fusion pro-tein group,nude mice in the MKK6(E)fusion protein+SB202190 group showed increased tumor volume,mass and serum CA125 levels,decreased tumor suppression and cancer cell apoptosis,better cancer cell status,decreased necrotic areas,increased expression of Fibronectin,MMP2 and MMP9,and down-regulated Bax and Cleaved caspase 3 expression was down-regulated,and Bcl-2 expression and p-p38/p38 and p-ATF-2/ATF-2 were up-regulated(P＜0.05).While p-ERK/ERK and p-JNK/JNK were compared among the 4 groups,the difference was not statistically significant(P＞0.05).Conclusion MKK6(E)fusion protein inhibits the growth of ovarian cancer subcutaneous graft tumors,and its mechanism may be related to the inhibition of p38/ATF-2 signa-ling pathway activation.
