The Sensitivity of Human Breast Cancer Stem Cells (ALDH+) Against Doxorubicin Treatment is Associated with PCNA and BIRC5 Gene Expressions

Introduction: Breast cancer stem cells (BCSCs) are identified as side populations in breast cancer cells owing stem cell properties and tumorigenic characteristics. Previous studies revealed that breast cancer chemotherapy led to BCSC enrichment which contributed to therapy resistance. Our recent in vivo study using Next Generation Sequencing has demonstrated that PCNA - the proliferative gene - and BIRC5 – the anti-apoptosis gene – were under-expressed in human breast tumors after neoadjuvant chemotherapy. This study aimed to verify the role of PCNA and BIRC5 expression in doxorubicin-treated human BCSCs in vitro and its association with cell viability. Method: Human BCSCs (ALDH+) were treated with 0.25 uM of doxorubicin for 2, 4, 6, 8, 10, 12, 14 days respectively. Cell viability was measured using trypan blue exclusion assay and the expressions of PCNA and BIRC4 mRNA were determined using qRT-PCR. Results: This study demonstrated that the viability of ALDH+ BCSCs decreased after 2 days and increased again after 8 days of doxorubicin treatment, indicating the decrease of doxorubicin sensitivity. Interestingly, PCNA and BIRC5 genes were modulated in line with the modulation of cell viability during doxorubicin treatment of human BCSCs. Conclusion: In conclusion, we suggest that the PCNA and BIRC5 expressions play an important role on the BCSCs viability which associated with the sensitivity of doxorubicin treatment.