Synergic effect of photodynamic therapy using talaporfin sodium with conventional anticancer chemotherapy for the treatment of bile duct carcinoma.

Abstract

BACKGROUND:

Photodynamic therapy (PDT) is an effective laser treatment for locally treating advanced bile duct carcinoma (BDC). The study objective was to evaluate the synergic effect of PDT using a new photosensitizer, talaporfin sodium (Laserphyrin), in combination with conventional anticancer drug treatments.

METHODS:

The range of the necrotic area, the percentage of apoptosis-positive cells, the vascular endothelial growth factor expression quantification, and the proliferating cell nuclear antigen-labeling index, as treatment effects, were examined in the BDC cell line (NOZ) in vitro and in vivo (4-wk-old male BALB/c mice).

RESULTS:

Tumor viability was determined by an in vitro MTS assay. PDT with a single treatment of 5-fluorouracil, gemcitabine, oxaliplatin, and cis-diamminedichloroplatinum showed a significantly lower viability compared with the control or the PDT-alone group (P<0.05). Furthermore, administering PDT combined with two anticancer drugs showed a further decline in the tumor viability. A treatment of PDT combined with oxaliplatin and gemcitabine showed the least viability (P<0.05). Thus, this regimen was administered in the in vivo study. The tumor necrotic area, apoptosis positivity, and the vascular endothelial growth factor expression rate were higher in the PDT with anticancer drugs group compared with those of the other groups (P<0.05). The proliferating cell nuclear antigen-labeling index results in the PDT with the anticancer drugs group were significantly lower than those of the other groups (P<0.05).

CONCLUSIONS:

A treatment of PDT combined with gemcitabine and oxaliplatin showed the best synergic effect for necrosis, apoptosis, and cytostatic alterations for the treatment of BDC.

• Authors: Yoshikazu Nonaka, Atsushi Nanashima, Takashi Nonaka, Masataka Uehara, Hajime Isomoto, Takafumi Abo, Takeshi Nagayasu
• Journal: The Journal of surgical research (J Surg Res) Vol. 181 Issue 2 Pg. 234-41 (May 2013) ISSN: 1095-8673 [Electronic] United States
• PMID: 22835954 (Publication Type: Evaluation Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Inc. All rights reserved.

Chemical References

• Antineoplastic Agents
• Biomarkers, Tumor
• Organoplatinum Compounds
• Photosensitizing Agents
• Porphyrins
• Proliferating Cell Nuclear Antigen
• Vascular Endothelial Growth Factor A
• vascular endothelial growth factor A, mouse
• Oxaliplatin
• Deoxycytidine
• Talaporfin
• Cisplatin
• Fluorouracil
• Gemcitabine

Topics

• Animals
• Antineoplastic Agents (administration & dosage)
• Antineoplastic Combined Chemotherapy Protocols (pharmacology, therapeutic use)
• Apoptosis (drug effects)
• Bile Duct Neoplasms (drug therapy, metabolism)
• Biomarkers, Tumor (metabolism)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Cisplatin (administration & dosage)
• Deoxycytidine (administration & dosage, analogs & derivatives)
• Drug Synergism
• Fluorouracil (administration & dosage)
• Humans
• Immunohistochemistry
• In Situ Nick-End Labeling
• Male
• Mice
• Mice, Inbred BALB C
• Organoplatinum Compounds (administration & dosage)
• Oxaliplatin
• Photochemotherapy
• Photosensitizing Agents (pharmacology, therapeutic use)
• Porphyrins (pharmacology, therapeutic use)
• Proliferating Cell Nuclear Antigen (metabolism)
• Treatment Outcome
• Vascular Endothelial Growth Factor A (metabolism)
• Gemcitabine