FBW7 increases drug sensitivity to cisplatin in human nasopharyngeal carcinoma by downregulating the expression of multidrug resistance-associated protein.

摘要: F-box/WD repeat-containing protein 7 (FBW7) is a member of the F-box family that regulates cell cycle progression and growth differentiation. FBW7 also functions as tumor suppressor. A cisplatin (CDDP)-based multidrug chemotherapy regimen standard for nasopharyngeal carcinoma (NPC), but drug resistance an increasing problem. Here, we evaluated relationship between resistance-associated (MRP), its correlation with in NPC, explored mechanism underlying to CDDP this disease. We used viability assays, Western blotting, small interfering RNA (siRNA) interference investigate NPC line. The expression MRP was detected by blotting after siRNA CDDP-resistant line, CNE2-CDDP. 3-(4 5-dimethyl-2-thiazolyl)-2 5-diphenyl-2-H-tetrazolium bromide (MTT) assay evaluate sensitivity various types antitumor drugs, including paclitaxel (PCX), CDDP, fluorouracil (5-FU), vincristine (VCR). found siRNA-mediated upregulation significantly increased chemosensitivity. IC50 values siRNA-FBW7-CNE2-CDDP FBW7-CNE2-CDDP-NC cells were 2.485 ± 0.155 4.867 ± 0.442 μmol/mL, respectively. PCX, 5-FU, VCR decreased siRNA-FBW7-CNE2 than FBW7-CNE2-NC (3.46 ± 0.14 vs. 46.21 ± 6.03 μmol/mL; 3.76 ± 0.54 39.45 ± 0.96 μmol/mL; 2.14 ± 1.67 28.76 ± 1.89 μmol/mL; 4.43 ± 0.89 87.90 ± 3.45 μmol/mL, respectively). less FBW7-CNE2-CDDP-NC. level CNE2 correlated downregulated MRP, cells.