Publikationsdatum:
2013-08-23
Beschreibung:
Transcription Factor E2F-1 plays a critical role in cell cycle regulation and other biological processes in cells. However whether or not it is involved in the multi-drug resistance (MDR) process of gastric cancer has not been fully elucidated yet. To explore the role of E2F-1 in the multi-drug resistance process of gastric cancer in vitro and in vivo , a cisplatin-resistant gastric cancer cell line with stable downregulation of E2F-1 was established. E2F-1 shRNA led to downregulation of endogenous E2F-1 mRNA and protein. It significantly promoted the sensitivity of SGC7901/DDP cells to cisplatin, doxorubicin, and fluorouracil. Flow cytometry confirmed that the percentage of apoptotic cells increased after E2F-1 downregulation. This notion was further supported by the observation that downregulation of E2F-1 blocked entry into the S-phase of the cell cycle. Furthermore, downregulation of E2F-1 significantly increased intracellular accumulation of doxorubicin. In addition, we determined the in vivo effects of E2F-1 small interfering RNA (shRNA) on tumor size, and apoptotic cells in tumor tissues were detected by deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling and hematoxylin and eosin staining. In molecular studies, semiquantitative RT-PCR and western blotting revealed that E2F-1 downregulation could inhibit expression of MDR1, MRP, Bcl-2/Bax, c-Myc, Skp2, Survivin and Cyclin D1. In comclusion: E2F-1 may be involved in regulating multiple signaling pathways in reversing MDR, suggesting that E2F-1 may represent a novel target for gastric cancer therapy. J. Cell. Biochem. © 2013 Wiley Periodicals, Inc.
Digitale ISSN:
0091-7419
Thema:
Biologie
,
Chemie und Pharmazie
,
Medizin
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