The
adenosine triphosphate-binding cassette (ABC) is a large group of
proteins involved in material transportation, cellular homeostasis, and closely associated with chemoresistance.
ATP-binding cassette
protein B4 (ABCB4) is a member of ABCs which has a similar structure to ABCB1, but fewer researches were performed. The present study is aimed to investigate the putative mechanism of ABCB4 in
5-fluorouracil (5-Fu) resistance. Then, we found that ABCB4 was significantly down-regulated in the
5-Fu resistant HCT8 cell lines by polymerase chain reaction (PCR) and Western blot. The knockdown of ABCB4 by
small interfering RNA decreased the apoptosis by
5-Fu in resistant HCT8R cell lines without influencing the proliferation. Also, we found a lower expression of cleaved
caspase and PARP by Western blot after the knockdown of ABCB4. However, the knockdown of ABCB4 did not influence the proliferation and apoptosis. Furthermore, the histological detection of ABCB4
mRNA level in human
colorectal cancer tissues and even in the recurrent tissues after
5-Fu single-agent
chemotherapy was employed to provide more concrete evidence that ABCB4 may be a tumor suppressor gene to regulate chemoresistance in
colorectal cancer. Moreover, a 109-patient cohort revealed that ABCB4 predicted a poor recurrence-free survival and overall survival. In summary, ABCB4 was down-regulated in the
5-Fu resistant cells and knockdown of ABCB4 alleviated the cell apoptosis and predicts a shorter recurrence-free survival and overall survival.