siRNA-mediated MDM2 inhibition sensitizes human lung cancer A549 cells to radiation

Wanfeng Guo, Kazi Mokim Ahmed, Yanpin Hui, Guozheng Guo, Jian-Jian Li

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

MDM2 (murine double minute 2) is well-documented to play a key role in radiation response and tumor radiosensitivity, thus offering an attractive clinic drug target to enhance tumor sensitivity to anti-cancer radiotherapy. In this study, we designed and tested two siRNA fragments against human MDM2 in non-small cell human lung cancer A549 cells. Transfection of mammalian expression vector pUR/U6 containing either MDM2 siRNA1 or siRNA2 fragment was shown to reduce MDM2 mRNA levels by 72% and 31%, respectively. Western blotting detected a similar inhibition of MDM2 protein levels in cells transfected with MDM2 siRNA1. A549 cells transfected with the expression vector for siRNA1 significantly decreased cell proliferation and rendered cells more sensitive to radiation. The basal apoptotic and necrotic cells, 1% and 2%, respectively, detected among A549 cells were increased to 2.6% and 14.4% after γ-irradiation with 5 Gy. Transfection of MDM2 siRNA1 induced 30.1% apoptosis and 12.7% necrosis while combined treatment of siRNA1 and 5-Gy radiation increased apoptosis and necrosis to 45.9% and 15.2%, respectively. These data provide the first evidence that specific siRNA fragment (MDM2 siRNA1) targeting human MDM2 mRNA is able to enhance lung cancer radiosensitivity.

Original languageEnglish (US)
Pages (from-to)1447-1452
Number of pages6
JournalInternational Journal of Oncology
Volume30
Issue number6
StatePublished - Jun 2007
Externally publishedYes

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Small Interfering RNA
Lung Neoplasms
Radiation Tolerance
Radiation
Transfection
Necrosis
Proto-Oncogene Proteins c-mdm2
Apoptosis
Radiation Dosage
Neoplasms
Messenger RNA
Non-Small Cell Lung Carcinoma
Radiotherapy
Western Blotting
Cell Proliferation
Pharmaceutical Preparations
A549 Cells
Therapeutics

Keywords

  • A549 cells
  • Ionizing radiation
  • MDM2
  • Radiosensitivity
  • siRNA

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

siRNA-mediated MDM2 inhibition sensitizes human lung cancer A549 cells to radiation. / Guo, Wanfeng; Ahmed, Kazi Mokim; Hui, Yanpin; Guo, Guozheng; Li, Jian-Jian.

In: International Journal of Oncology, Vol. 30, No. 6, 06.2007, p. 1447-1452.

Research output: Contribution to journalArticle

Guo, Wanfeng ; Ahmed, Kazi Mokim ; Hui, Yanpin ; Guo, Guozheng ; Li, Jian-Jian. / siRNA-mediated MDM2 inhibition sensitizes human lung cancer A549 cells to radiation. In: International Journal of Oncology. 2007 ; Vol. 30, No. 6. pp. 1447-1452.
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