Down-regulation of FOS-like antigen 1 enhances drug sensitivity in breast cancer

Abstract

Objective: Multidrug resistance (MDR) to chemotherapeutic drugs is an important reason for clinical chemotherapy failure. So far, the relationship between FOS-like antigen1 (FOSL1) and chemotherapy sensitivity of breast cancer remains unclear. This study investigates the relationship between FOSL1 and chemotherapy sensitivity of breast cancer and its molecular mechanism.

Methods: Doxorubicin-resistant MCF-7/ADR breast cancer cells were transfected with NC (control) or FOSL1 siRNA and assayed for cell viability and relative colony number by MTT assay and colony formation, respectively. The expression level of FOSL1 was detected by immunohistochemistry (IHC). The relationship between FOSL1 and chemotherapy sensitivity was analyzed by a one-way of variance analysis and Pearson's chi-square test among a total of 50 patients with stage II and III breast cancer before and after they received epirubicin-based neoadjuvant chemotherapy (NCT) between 2012 and 2017.

Results: The expression of FOSL1 was increased in breast cancer tissues compared with normal breast tissues (P<0.05), and the expression of FOSL1 was decreased after NCT treatment compared with breast cancer tissues (or before NCT). This lower expression of FOSL1 was correlated with chemotherapy resistance or chemotherapy sensitivity (P<0.05). Moreover, the expression level of FOSL1 was markedly lower in NCT-sensitive patients than that of NCT-resistant patients (P<0.05).

Conclusion: Down-regulation of FOSL1 potentiated chemotherapy sensitivity of breast cancer, and its lower expression attenuated chemotherapeutic drug resistance in human breast cancer cells. FOSL1 might be a drug target for predicting chemotherapy effect in breast cancer.

Keywords: FOSL1; breast cancer; chemotherapy resistance; chemotherapy sensitivity; doxorubicin.

Figure 1

Down-regulation of FOSL1 weakened doxorubicin resistance of MCF-7/ADR cells and suppressed cell growth and proliferation. A. MTT assay was performed to test cell proliferation after siFOSL1 was transfected into MCF-7/ADR cells compared to negative control before and after co-culturing with doxorubicin. B. Soft agar colony forming assay was used to evaluate the relative colony number of siFOSL1 or siNC transfected into MCF-7/ADR cells separately before and after co-culturing with doxorubicin. *P<0.05 compared with siNC group or siNC group treated by doxorubicin. **P<0.01 compared with siNC group or siNC group treated by doxorubicin.

Figure 2

Immumohistochemical staining was performed to test the level of FOSL1 in breast cancer tissues before and after neoadjuvant chemotherapy (×100). A. Expression of FOSL1 in normal breast tissues was low. B. Expression of FOSL1 in breast cancer tissues was high compared to normal breast cancer tissues. C. Expression of FOSL1 was lower after neoadjuvant chemotherapy of breast cancer compared with before neoadjuvant chemotherapy (or breast cancer tissues). D. There was no FOSL1 expression in the negative control group (PBS instead of primary antibody).