Flap endonuclease 1 silencing is associated with increasing the cisplatin sensitivity of SGC‑7901 gastric cancer cells.

Abstract

Flap endonuclease 1 (FEN1), which is key in DNA replication and repair, has been demonstrated to be intimately involved in the development and progression of cancer. Our previous study determined that the downregulation of FEN1 can suppress the proliferation of, and induce apoptosis in, gastric cancer SGC‑7901 cells. In addition, several FEN1 inhibitors have been identified to increase sensitisation to DNA injury agents. These results may provide a promising treatment method to enhance the traditional chemotherapeutics used for the treatment of gastric cancer. Thus, the aim of the present study was to determine the role of FEN1 in the chemosensitivity of SGC‑7901 cells. The protein expression levels of FEN1 in cisplatin (CDDP)‑treated SGC‑7901 cells were detected using western blot analysis. FEN1 was silenced via specific FEN1‑targeted small interfering RNAs (siRNA). The survival and apoptotic rates of the SGC‑7901 cells were assessed using an MTT assay and flow cytometry, respectively. Relevant apoptotic factors were detected using western blotting. The results showed that the expression of FEN1 was significantly induced by CDDP in a dose‑ and time‑dependent manner. The targeting of FEN1 in SGC‑7901 cells, in combination with CDDP treatment, significantly inhibited their proliferation and effectively increased their apoptotic rate. In addition, in the cells targeted with FEN1‑siRNA and exposed to CDDP, the levels of Bcl‑2‑associated X protein were significantly increased, whereas the expression levels of Bcl‑2 and Bcl‑extra large were effectively decreased, compared with the cells exposed to negative control‑siRNA and CDDP. These results suggest a potential chemotherapeutic target, which exhibits enhanced sensitivity to CDDP following FEN1 silencing in SGC‑7901 cells via decreased survival and increased apoptosis.

• Authors: Chunhong Xie, Kejia Wang, Daorong Chen
• Journal: Molecular medicine reports (Mol Med Rep) Vol. 13 Issue 1 Pg. 386-92 (Jan 2016) ISSN: 1791-3004 [Electronic] Greece
• PMID: 26718738 (Publication Type: Journal Article)

Chemical References

• RNA, Small Interfering
• bcl-2-Associated X Protein
• bcl-X Protein
• Flap Endonucleases
• Cisplatin

Topics

• Apoptosis (drug effects)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Cisplatin (pharmacology)
• Flap Endonucleases (metabolism)
• Gene Silencing (drug effects)
• Humans
• RNA, Small Interfering (metabolism)
• Stomach Neoplasms (enzymology, pathology)
• Up-Regulation (drug effects)
• bcl-2-Associated X Protein (metabolism)
• bcl-X Protein (metabolism)