Myeloid differentiation protein 2 affects paclitaxel resistance in triple-negative breast cancer by regulating EGFR signaling pathway
10.3760/cma.j.cn.115807-20220315-00062
- VernacularTitle:髓样分化蛋白2通过调控EGFR信号通路影响三阴性乳腺癌紫杉醇耐药性
- Author:
Shurong ZHENG
1
;
Qidi HUANG
;
Weida FU
;
Kangkang LU
;
Guilong GUO
Author Information
1. 温州医科大学附属第一医院乳腺外科，温州 325000
- Keywords:
Triple negative breast cancer;
Myeloid differentiation protein 2;
Drug resistance;
EGFR signaling pathway
- From:
Chinese Journal of Endocrine Surgery
2022;16(3):309-313
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the effects of myeloid differentiation protein-2 (MD-2) on paclitaxel resistance cells in triple negative breast cancer (TNBC) through EGFR signaling pathway.Methods:Immunohistochemical method was used to detect the expression of MD-2 in cancer tissue and adjacent tissue of TNBC patients, and the relationship between MD-2 expression and clinicopathological parameters of patients was analyzed. The TNBC paclitaxel-resistant cell line was constructed and MD-2 expression in cells was interfered. Cell invasion was detected by Transwell, and cell apoptosis was detected by flow cytometry. The signaling pathways regulated by MD-2 were screened by transcriptome sequencing and verified by Western blot.Results:The expression of MD-2 was significantly enhanced in cancer tissues relative to adjacent tissues. High expression of MD-2 was closely related to clinical stage, tumor size, tumor recurrence and metastasis ( χ2=4.50, P=0.032; χ2=2.55, P=0.011; χ2=4.40, P=0.036). In cell experiments, compared with normal breast cells, the expression of MD-2 in TNBC cell lines was significantly enhanced. Compared with sh-NC group (100±11.52) (6.81±0.57), knockdown of MD-2 could inhibit the invasion (61.44±6.78) ( t=4.99, P=0.008) but promote apoptosis (15.19±1.06) ( t=12.06, P<0.001) of paclitaxel resistant TNBC cells. Transcriptome sequencing and Western blot results showed that MD-2 mainly affects the biological behavior of TNBC cells by regulating the EGFR signaling pathway. Conclusions:MD-2 promoted TNBC cell invasion and paclitaxel resistance, which may be achieved by affecting the EGFR signaling pathway. MD-2 is expected to become an effective target in TNBC treatment.
