The role and mechanism of HOXD3 in the stemness and chemotherapy resistance of breast cancer cells
10.3969/j.issn.1000-8179.2018.12.194
- VernacularTitle:HOXD3在乳腺癌细胞干性和化疗耐药性中的作用及机制研究
- Author:
Yanxia HE
1
;
Jun YAN
;
Hongbin LI
;
Qingyuan ZHANG
;
Shaoqiang CHENG
;
Yue ZHANG
Author Information
1. 哈尔滨医科大学附属肿瘤医院乳腺淋巴内科 哈尔滨市150081
- Keywords:
HOXD3;
breast cancer;
cancer stem cells;
drug resistance;
integrin β3
- From:
Chinese Journal of Clinical Oncology
2018;45(12):614-619
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To investigate the effect of HOXD3 expression on the stem cell-like characteristics of breast cancer cells and the relationship between HOXD3 expression and multi-drug resistance in breast cancer cells. Methods: From January 2006 to December 2008, 87 specimens of breast cancer patients from the Affiliated Tumor Hospital of Harbin Medical University were collected. The ex-pression of HOXD3 in breast cancer cells and tissues was detected by immunohistochemical staining method. The expression levels of HOXD3 in CDDP or DOX-resistant cell lines MDA-MB-231 and MDA-MB-435 were detected by RT-PCR, Western blot and immunofluo-rescence staining. The effect of HOXD3 overexpression on the expression levels of stem cell biomarkers in breast cancer cell lines MDA-MB-231 and MDA-MB-435 was analyzed. MTT assay and colony formation assay were used to demonstrate the role of HOXD3 in che-motherapy resistance of breast cancer cells. Results: The relative expression of HOXD3 mRNA in breast cancer was 4.16, which was sig-nificantly higher than 2.05 in normal tissues adjacent to cancer; the relative expression levels of HOXD3 mRNA in breast cancer cell lines MDA-MB-231, MDA-MBB-435 and MCF-7 were 3.25, 2.84 and 2.23, which were all higher than 1.00 in normal breast epithelial cell line MCF-10A ( all P＜0.05 ). The IC50s of MDA-MB-231 and MDA-MB-435 cell lines resistant to CDDP or DOX were (20.82±0.05) μmol/L, (19.69±0.47) μmol/L, (32.26±0.23) mmol/L and (26.08±0.55) mmol/L, respectively. Both were higher than the corresponding original cell lines (all P＜0.05), and the drug resistance times were 2.47 and 3.10 or 1.86 and 2.08, respectively. The number of tumor spheres and stem cell biomarker expression levels of MDA-MB-231 and MDA-MB-435 with HOXD3 overexpression were significantly in-creased (all P＜0.05). Conclusions: The expression of HOXD3 plays an important role in the maintenance of stem cell-like properties and drug resistance of breast cancer cells. The results of this study will help us better understand the complexity of breast cancer and pro-vide a theoretical basis for the development of targeted molecular therapy.
