Suppression of LRP16 gene expression decreased the lethal sensitivity of MCF-7 cell line to 5-FU

objective: To explore the effect of the human gene LRP16 on MCF-7 cell proliferation and the potential clincial significance. Methods: Three MCF-7 human breast cancer cell lines with different LRP16 expression level by retrovirus-mediated siRNA strategy, pL374（suppressive rate 90%）, pL668（suppressive rate 60%） and pGFPi（negative control） were used as model cells. Cell proliferation assay were performed by using trypan blue exclusion method. 5-FU, a typical S phase specific chemotherapeutic drug, was used to induced cell death. The cell viability of the pL374, pGFPi cell lines was also assayed. Results: The proliferative ability of pGFPi, pL668 and pL374 cell lines were significantly decreased in order（P＜0.05）. After being treated with 5-FU, pGFPi cells died more than 10 percent at 24 h time point, 20 percent at 48 h,75 percent at 72 h and nearly 100 percent at 96 h. In contrast with the control cells, 5-FU did not markedly induced the pL374 cells death until 72 h, only 30 percent at 96 h.Conclusions: Inhibition of LRP16 gene expression in MCF-7 cells effective suppressed cells proliferative ability and decreased the lethal sensitivity to 5-FU. These results indicated that LRP16 gene involves in the regulation of MCF-7 cell cycle transition, possibly by modulating the G₁/S checkpoints. Taken together, LRP16 gene might play important roles in tumorgenicity and progression, and maybe a candidate therapeutic target of estrogen-dependent breast cancer.