Suppression of OCT4B enhances sensitivity of lung adenocarcinoma A549 cells to cisplatin via increased apoptosis

Anticancer Res. 2013 Dec;33(12):5365-73.

Abstract

Background: Resistance to chemotherapy in lung adenocarcinoma remains a major obstacle. We examined the potential role of Octamer-binding transcription factor-4B (OCT4B) in enhancing sensitivity of lung adenocarcinoma cells to cisplatin.

Materials and methods: RNAi interference was used to examine the role of OCT4B in cisplatin-treated A549 cells. Cells were transfected with OCT4B siRNA prior to a 48-h cisplatin treatment. Propidium iodide (PI) and caspase-3 staining were used to determine cell viability and apoptosis. Cell-cycle analysis was performed to evaluate alterations in phase distribution.

Results: OCT4B suppression in cells increased the number of non-viable, PI(+), and apoptotic, caspase-3(+) cells in the presence and absence of cisplatin treatment. Importantly, cisplatin treatment of OCT4B-suppressed cells resulted in a marked transition of cells from G0/G1 to G2/M phase.

Conclusion: Silencing of OCT4B confers sensitivity to cisplatin treatment in A549 cells via cell-cycle regulation, increased proliferation and enhancement of cisplatin-induced apoptosis. OCT4B clearly protects A549 cells from apoptosis.

Keywords: A549; OCT4B; apoptosis; chemoresistance; cisplatin.

MeSH terms

  • Adenocarcinoma / pathology*
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Base Sequence
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cisplatin / pharmacology*
  • DNA Primers
  • Humans
  • Lung Neoplasms / pathology*
  • Octamer Transcription Factor-3 / genetics*
  • RNA, Small Interfering / genetics
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Antineoplastic Agents
  • DNA Primers
  • Octamer Transcription Factor-3
  • POU5F1 protein, human
  • RNA, Small Interfering
  • Cisplatin