Adenovirus-mediated p53 treatment enhances photodynamic antitumor response.
Photodynamic therapy (PDT) has been reported to be effective for treating various tumors and to induce apoptosis in many tumor cells. In this study, we evaluated the ability of PDT combined with a tumor suppressor factor, recombinant adenovirus p53 (AdCMVp53), to induce apoptosis as well as cell growth inhibition in CaSki human cervical cancer cells and in nude mice with implanted CaSki cells. To examine levels of apoptosis, CaSki cells were treated with PDT and/or AdCMVp53, and an annexin V-staining assay was then conducted. In addition, Western blot analysis was done to identify p53 induction at the cellular and tumor tissue levels. PDT+AdCMVp53 cotreatment caused remarkable inhibition of CaSki cell proliferation, as compared with the individual treatments. In parallel with the inhibition of cell proliferation, the cotreatment caused a significantly greater increase in the annexin V-stained cell population compared with the individual treatments, as determined by fluorescence-activated cell-sorting analysis. The Western blotting assay also showed significantly more cellular p53 expressed after PDT+AdCMVp53 cotreatment than after each separate treatment. This was consistent with observations of tumor tissue in the mouse system. However, apoptosis- related protein, p21, was significantly suppressed by PDT+AdCMVp53 cotreatment, contrary to treatment with AdCMVp53 alone. Taken together, these findings suggest that PDT plus AdCMVp53 gene therapy exerts more potent antitumor effects on human cervical cancer cells, with induction of apoptosis at least through activation in p53 protein at the cellular and tumor tissue levels.
Lim
Dae-Seog
DS
Cancer Research Institute of Medical Science, The Catholic University of Korea, Seoul 137-040, South Korea.
Bae
Su-Mi
SM
Kwak
Sun-Young
SY
Park
Eun-Kyung
EK
Kim
Jong-Ki
JK
Han
Sei-Jun
SJ
Oh
Chung-Hun
CH
Lee
Chang-Hee
CH
Lee
Won-Young
WY
Ahn
Woong-Shick
WS
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D017209:Apoptosis / Q000502:physiology / Q000528:radiation effects; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000528:radiation effects; D003131:Combined Modality Therapy; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000627:therapeutic use*; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D023041:Xenograft Model Antitumor Assays
D017319:Photosensitizing Agents; D016159:Tumor Suppressor Protein p53