Tuberc Respir Dis.  2007 Jul;63(1):52-58. 10.4046/trd.2007.63.1.52.

Gene Expression Profile of Lung Cancer Cells Following Photodynamic Therapy

Affiliations
  • 1Department of Molecular and Cellular Biochemistry, College of Medicine, Kangwon National University, Korea.
  • 2Clinical Research Institute of Kangwon National University Hospital, Korea.
  • 3Department of Internal Medicine, College of Medicine, Kangwon National University, Chunchon, Korea. pulmo2@kangwon.ac.kr

Abstract

BACKGROUND: Photodynamic therapy is a viable option for lung cancer treatment, and many studies have shown that it is capable of inducing cell death in lung cancer cells. However, the precise mechanism of this cell death has not been fully elucidated. To investigate the early changes in cancer cell transcription, we treated A549 cells with the photosensitizer DH-I-180-3 and then we illuminated the cells.
METHODS
We investigated the gene expression profiles of the the A549 lung cancer cell line, using a DEG kit, following photodynamic therapy and we evaluated the cell viability by performing flow cytometry. We identified the genes that were significantly changed following photodynamic therapy by performing DNA sequencing.
RESULTS
The FACS data showed that the cell death of the lung cancer cells was mainly caused by necrosis. We found nine genes that were significantly changed and we identified eight of these genes. We evaluated the expression of two genes, 3-phosphoglycerate dehydrogenase and ribosomal protein S29. The expressed level of carbonic anhydrase XII, clusterin, MRP3s1 protein, complement 3, membrane cofactor protein and integrin beta 1 were decreased.
CONCLUSION
Many of the gene products are membrane-associated proteins. The main mechanism of photodynamic therapy with using the photosensitizing agent DH-I-180-3 appears to be necrosis and this may be associated with the altered production of membrane proteins.

Keyword

Gene expression profiling; Lung neoplasms; Photosensitizing agents

MeSH Terms

Antigens, CD46
Carbonic Anhydrases
Cell Death
Cell Line
Cell Survival
Clusterin
Complement System Proteins
Flow Cytometry
Gene Expression Profiling
Gene Expression*
Lung Neoplasms*
Lung*
Membrane Proteins
Necrosis
Phosphoglycerate Dehydrogenase
Photochemotherapy*
Photosensitizing Agents
Ribosomal Proteins
Sequence Analysis, DNA
Transcriptome*
Antigens, CD46
Carbonic Anhydrases
Clusterin
Complement System Proteins
Membrane Proteins
Phosphoglycerate Dehydrogenase
Photosensitizing Agents
Ribosomal Proteins

Figure

  • Figure 1 Quantitative analysis of the apoptotic and necrotic cells. A549 cells were analyzed 1, 2, 3, and 12h following PDT. While no increase in apoptotic or necrotic cells was seen with the photosensitizer only, about 50% were necrotic till 3h and about 30% were necrotic by 12h. FACS data showed that the mechanism of cell death is mainly necrosis.

  • Figure 2 Differential expression of genes in agarose gel with or without PDT. Two bands increased (arrow 1,6) and seven decreased following PDT (arrow 2-5,7-9). (1; pre-PDT, 2; post-PDT, GP; GeneFishing primer)


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