No abstract

Breast cancer (BC), which is widely considered as the most common cancer in women around the world, evokes ~1.7 million new BC cases and 522,000 BC‐related deaths each year. Triple negative breast cancer (TNBC) is clinically confirmed as one of the most aggressive subtypes of BC. ORY‐1001, a clinically used lysine specific demethylase 1 (LSD1/KDM1A) inhibitor, was investigated herein to confirm its role in the progression of TNBC and reveal the potential mechanism. After treatment with ORY‐1001 in MDA‐MB‐231 and BT549 cells, the cell proliferation and apoptosis were respectively measured by CCK‐8 and TUNEL assays. The expression of proliferation‐ and apoptosis‐associated proteins was tested by means of western blot analysis. Then, R1881, an androgen receptor (AR) agonist, was used to evaluate whether the effects of ORY‐1001 on proliferation and apoptosis of TNBC cells was mediated by regulating AR. Results indicated that ORY‐1001 treatment restrained the proliferation while enhanced the apoptosis of BC cells, accompanied by the change of proliferation‐ and apoptosis‐related proteins expression. Furthermore, ORY‐1001 reduced the level of AR in BC cells. After the activation of AR by R1881, the decreased proliferation and enhanced apoptosis of BC cells triggered by ORY‐1001 intervention were partially abolished. In conclusion, this paper has presented the first evidence to suggest that ORY‐1001 inhibits proliferation and promotes apoptosis of TNBC cells by suppressing AR expression, which may constitute the theoretical basis for the clinical use of ORY‐1001 in the treatment of this disease.

No abstract

Breast cancer is one of the most common malignant tumors in women. Cell division cycle-associated 5 (CDCA5) is closely associated with the behavior of various cancer types. The aim of the present study was to explore the effect of CDCA5 on breast cancer. Western blot analysis and reverse transcription-quantitative PCR were used to detect the expression level of CDCA5 in human normal mammary cells and human breast cancer cell lines. To determine its function in MDA-MB-231 cells, CDCA5 was silenced in MDA-MB-231 cells by transient short hairpin RNA transfection. Cell Counting Kit-8 and clonogenicity assays were used to evaluate cell proliferation. Wound healing and Transwell assays were used to detect cell invasion and migration. Western blot analysis was used to detect the protein expressions of Ki67 and PCNA associated with proliferation, MMP2 and MMP9 associated with migration. CDCA5 was found to be markedly increased in breast cancer cell lines. CDCA5 knockdown was able to suppress cell proliferation, invasion and migration. CDCA5 inhibition downregulated PDS5 cohesin-associated factor A (PDS5A) expression in breast cancer cells. PDS5A overexpression was found to reverse the effect of CDCA5 inhibition on breast cancer cell proliferation and migration. CDCA5 knockdown was shown to suppress the malignant progression of breast cancer cells by regulating PDS5A. The present findings may provide new potential targets for breast cancer therapy.