Abstract:
Objective To investigate the effect of HOXD3 expression on the stem cell-like characteristics of breast cancer cells and therelationship between HOXD3 expression and multi-drug resistance in breast cancer cells.
Methods From January 2006 to December2008, 87 specimens of breast cancer patients from the Affiliated Tumor Hospital of Harbin Medical University were collected. The expression of HOXD3 in breast cancer cells and tissues was detected by immunohistochemical staining method. The expression levels ofHOXD3 in CDDP or DOX-resistant cell lines MDA-MB-231 and MDA-MB-435 were detected by RT-PCR, Western blot and immunofluorescence staining. The effect of HOXD3 overexpression on the expression levels of stem cell biomarkers in breast cancer cell lines MDAMB-231 and MDA-MB-435 was analyzed. MTT assay and colony formation assay were used to demonstrate the role of HOXD3 in chemotherapy resistance of breast cancer cells.
Results The relative expression of HOXD3 mRNA in breast cancer was 4.16, which was significantly higher than 2.05 in normal tissues adjacent to cancer; the relative expression levels of HOXD3 mRNA in breast cancer celllines 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 epithelialcell 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 correspondingoriginal 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 tumorspheres and stem cell biomarker expression levels of MDA-MB-231 and MDA-MB-435 with HOXD3 overexpression were significantly increased (all P < 0.05).
Conclusions The expression of HOXD3 plays an important role in the maintenance of stem cell-like properties anddrug resistance of breast cancer cells. The results of this study will help us better understand the complexity of breast cancer and provide a theoretical basis for the development of targeted molecular therapy.