A possible relationship between the anti-cancer potency of photodynamic therapy using the novel photosensitizer ATX-s10-Na(II) and expression of the vascular endothelial growth factor in vivo.
ATX-s10-Na(II) is a novel second-generation photo-sensitizer for photodynamic therapy (PDT). PDT using ATX-s10 and diode laser (670 nm) induces an apoptotic response, inflammatory reaction, immune reaction and damage to the microvasculature. In particular, the vascular shut-down effect plays an important role in the anti-tumor activity of ATX-s10-PDT. It has been reported that PDT induces hypoxia and expression of the vascular endothelial growth factor (VEGF) via the hypoxia-inducible factor 1 (HIF1)-alpha pathway. We hypothesized that the expression of VEGF may cause tumor recurrence after PDT and exert unfavorable effect against the anti-tumor activity of ATX-s10-PDT. In this study, we showed by DNA microarray analysis in vitro that VEGF mRNA expression was induced 3 h after laser irradiation in ATX-s10-PDT. We compared the anti-tumor activity of ATX-s10-PDT against lung cancer cell lines SBC-3 and SBC-3/VEGF, the latter overexpressing VEGF; there was no significant difference in the sensitivity to the PDT between the two cell lines as assessed by clonogenic assay. Furthermore, no statistically significant difference in the anti-tumor effect of PDT, as measured by tumor cures, was found between SBC-3 and SBC-3/VEGF tumors in female Balb/c-nu/nu nude mice in vivo. In conclusion, ATX-s10-PDT may prevent tumor recurrence despite induction of VEGF and promotion of tumor angiogenesis, which are known to enhance tumor proliferation and survival.
Respiratory Disease Center, Sanno Hospital, International University of Health and Welfare, Tokyo, Japan.
T
T
Okunaka
J
J
Usuda
S
S
Ichinose
H
H
Hirata
K
K
Ohtani
S
S
Maehara
T
T
Inoue
K
K
Imai
M
M
Kubota
Y
Y
Tsunoda
Y
Y
Kuroiwa
H
H
Tsutsui
K
K
Furukawa
K
K
Nishio
H
H
Kato
D000818:Animals; D045744:Cell Line, Tumor; D004273:DNA, Neoplasm / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D008175:Lung Neoplasms; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D020411:Oligonucleotide Array Sequence Analysis; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000627:therapeutic use*; D011166:Porphyrins / Q000627:therapeutic use*; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
C117772:ATX S10Na(II); D004273:DNA, Neoplasm; D017319:Photosensitizing Agents; D011166:Porphyrins; D042461:Vascular Endothelial Growth Factor A; D012313:RNA