Antitumor Effect of 5-Aminolevulinic Acid Methyl Ester-Mediated Photodynamic Therapy on Local Skin Melanoma and Its Metastasized Tumor, in Relation with Antitumor Immunity.

UNLABELLED: Objective of the present study is to investigate the effect of photodynamic therapy (PDT) mediated by 5-aminolevulinic acid methyl ester hydrochloride (ALA-Me) on inhibiting the primary tumor growth and metastasis of melanoma, in relation with antitumor immunity. Although the effect of ALA-PDT on lymphocyte T cells has been extensively studied, there are limited publications about ALA-PDT effect on B cells and NK cells. In particular, at present there is no study of ALA-Me-PDT on B cells and NK cells. Therefore, in order to only investigate this aspect, we have employed T-lymphocyte deficient Balb/c nude mice.

METHODS

A non-pigmented melanoma mouse model, which was challenged with human primary melanoma cells WM266-4, was established in 36 nude mice. When the melanoma grew to size of (0.4 ȕ 0.4) cm2, the 36 mice were randomly divided into 4 groups, i.e., ALA-Me intravenous (i.v.) injection-PDT, ALA-Me intraperitoneal (i.p.) injection-PDT, ALA-Me topical application-PDT and control group without any treatment. The dose for systemic administration (i.v. and i.p.) of ALA-Me was 250 mg/kg. For topical application of ALA-Me, a cream with 25 mg/cm2 was smeared on the tumor tissue. The tumor site was irradiated by the red light from LEDs lamp with fluence rate 90 mW/cm2 and energy rate 50 J/cm2.

RESULTS

The inhibitory effects on both tumor growth and metastasis were observed after all three treatments mentioned above. In terms of inhibiting tumor growth, there was a significant difference in the volume of tumor between the treatment groups and the control group (P < 0.05). Furthermore, a very significant (P < 0.01) inhibitory effect on tumor lung metastasis was found after the three treatments. Moreover, the ALA-Me-PDT-induced immune response was also observed by means of increase of immune cells NK cells in the spleen of the T cell-deficient nude mice.

CONCLUSION

ALA-Me-PDT had significant inhibitory effects both on local tumor growth and distant lung metastasis of melanoma. There was also significant antitumor immunity caused by ALA-Me-PDT. Results of the present study provide a potential possibility for ALA-Me-PDT in the treatment of skin melanoma and its metastasis.