Paclitaxel augments cytotoxic effect of photodynamic therapy using verteporfin in gastric and bile duct cancer cells.
Photodynamic therapy (PDT) shows a limited antitumor effect in treating gastrointestinal tumors because of improper light penetration or insufficient photosensitizer uptake. The aim of this study was to evaluate the cytotoxic effect of PDT combined with paclitaxel on in vitro cancer cells. In vitro photodynamic therapy was performed in gastric cancer cells (NCI-N87) and bile duct cancer cells (YGIC-6B) using verteporfin (2 ug mL(-1)) and a PTH light source (1 000 W, Oriel Co.) with 665-675 nm narrow band pass filter. Cytotoxicity was compared using the MTT assay between cancer cells treated with PDT alone or pretreated with paclitaxel (IC(25)). Apoptotic changes were evaluated using DAPI staining, DNA fragmentation analysis, Annexin V-FITC apoptosis assay, cell cycle analysis, and western blots for cytochrome c, Bax, and Bid. The PDT-induced cytotoxicity was potentiated by pretreating with low dose paclitaxel (P < 0.001). The enhanced cytotoxicity was due to an augmented apoptotic response mediated by exaggerated cytochrome c released from mitochondria, without Bax or Bid activation. These results show that paclitaxel pretreatment enhances PDT-mediated cancer therapy.
Park
Seungwoo
S
Department of Internal Medicine, Yonsei University College of Medicine, Seodaemun-Gu, 120-752, Seoul, South Korea.
Hong
Sung Pil
SP
Oh
Tae Yoon
TY
Bang
Seungmin
S
Chung
Jae Bock
JB
Song
Si Young
SY
D017209:Apoptosis / Q000187:drug effects; D001650:Bile Duct Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D045304:Cytochromes c / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D017239:Paclitaxel / Q000494:pharmacology* / Q000633:toxicity; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology* / Q000627:therapeutic use; D011166:Porphyrins / Q000494:pharmacology* / Q000627:therapeutic use; D013274:Stomach Neoplasms / Q000473:pathology*; D000077362:Verteporfin
D017319:Photosensitizing Agents; D011166:Porphyrins; D000077362:Verteporfin; D045304:Cytochromes c; D017239:Paclitaxel