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.
Okunaka
T
T
Respiratory Disease Center, Sanno Hospital, International University of Health and Welfare, Tokyo, Japan.
Usuda
J
J
Ichinose
S
S
Hirata
H
H
Ohtani
K
K
Maehara
S
S
Inoue
T
T
Imai
K
K
Kubota
M
M
Tsunoda
Y
Y
Kuroiwa
Y
Y
Tsutsui
H
H
Furukawa
K
K
Nishio
K
K
Kato
H
H
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