[Effects of 5-aminolevulinic acid photodynamic therapy on cervical cancer: in vivo experiment with nude mice].
OBJECTIVE
To study the effects of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) on human cervical cancer, and to identify the best administration regimen with the least phototoxic reaction.


METHODS
Seventy-two BALB/c nude mice underwent subcutaneous injection of human cervical cancer cells of the line Me180 so as to establish animal models, and then randomly divided into 6 equal groups: pure topical administration group (undergoing injection of ALA 60 mg/kg around the tumor), pure intravenous administration group (undergoing injection of ALA 250 mg/kg into the caudal vein), topical administration and PDT group (undergoing injection of ALA 60 mg/kg around the tumor and radiotherapy of 630 nm He-Ne laser 6 h after the drug administration), intravenous administration and PDT group (undergoing injection of ALA 250 mg/kg into the caudal vein and radiotherapy of 630 nm He-Ne laser 6 h after the drug administration), and control group (undergoing none of the treatment). 24 h later 6 mice from each group were killed with their tumors taken out. On the days 3, 7, 14, and 21 after treatment the remaining mice underwent measurement of the tumor size. HE staining and pathological examination were performed. Immunohistochemical study was conducted to detect the protein expression of the apoptosis-inhibiting genes of survivin and vascular endothelial growth factor (VEGF). RT-PCR was used to detect the mRNA expression of the apoptosis-inhibiting gene of Bcl-2 and apoptosis-promoting genes of P53, Bax, and Bad.


RESULTS
The tumor volumes after treatment of the pure topical administration and pure caudal vein administration groups were (0.09 +/- 0. 02) cm3 and (0.14 +/- 0.04) cm3 respectively, both significantly smaller than that of the control group [(0.67 +/- 0.06) cm3, both P < 0.01]. The tumor volume of the pure topical administration group 7-14 days after treatment was the smallest. HE staining showed remarkable subcutaneous necrosis in the 2 PDT groups. Immunohistochemistry showed remarkable down-regulation of protein expression of survivin and VEGF in the PDT groups. RT-PCR showed that the mRNA expression levels of survivin and Bcl-2 were both significantly lower than that of the control group (both P < 0.01), and the mRNA expression levels of P53, Bax, and Bad were higher than those of the control group, however, not significantly (all P > 0.05).


CONCLUSIONS
ALA-PDT is effective in treatment of cervical cancer. Topical ALA administration + PDT is recommended in treating cervical cancer so as to minimize the side-effects and inconvenience of phototoxic reaction brought by PDT.
He
Gui-fang
GF
Department of Gynecology, China-Japan Friendship Hospital, Beijing 100029, China.
Bian
Mei-lu
ML
Zhao
Ya-wei
YW
Xiang
Qing
Q
Li
Hong-yan
HY
Xiao
Cheng
C
D000622:Aminolevulinic Acid / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis; D010778:Photochemotherapy; D000077022:Survivin; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis; D023041:Xenograft Model Antitumor Assays
C516989:Birc5 protein, rat; D008869:Microtubule-Associated Proteins; D000077022:Survivin; D042461:Vascular Endothelial Growth Factor A; D000622:Aminolevulinic Acid