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. 2019 Jun;17(6):5132-5138.
doi: 10.3892/ol.2019.10198. Epub 2019 Mar 29.

Radiosensitizing effect of 5-aminolevulinic acid in colorectal cancer in vitro and in vivo

Kazuto Yamada  1 , Yasutoshi Murayama  1 , Yosuke Kamada  1 , Tomohiro Arita  1 , Toshiyuki Kosuga  1 , Hirotaka Konishi  1 , Ryo Morimura  1 , Atsushi Shiozaki  1 , Yoshiaki Kuriu  1 , Hisashi Ikoma  1 , Takeshi Kubota  1 , Masayoshi Nakanishi  1 , Hitoshi Fujiwara  1 , Kazuma Okamoto  1 , Eigo Otsuji  1
Affiliations
Free PMC article

Radiosensitizing effect of 5-aminolevulinic acid in colorectal cancer in vitro and in vivo

Kazuto Yamada et al. Oncol Lett. 2019 Jun.
Free PMC article

Abstract

The radiosensitizing effect of 5-aminolevulinic acid (5-ALA) has been demonstrated in glioma and melanoma in a number of studies. Enhancing the radiosensitivity of colorectal cancer may improve survival rates and lessen adverse effects. The present study assessed the radiosensitizing effect of 5-ALA in colorectal cancer using the human colon cancer cell line HT29 in vitro and in vivo. In vitro, cells were pretreated with 5-ALA and exposed to ionizing radiation. Cells pretreated with or without 5-ALA were compared using a colony formation assay. In vivo, HT29 cells were implanted into mice subcutaneously and subsequently exposed to ionizing radiation. 5-ALA was administrated by intraperitoneal injection. Subcutaneous tumors treated with or without 5-ALA were compared. Single-dose and multi-dose irradiations were applied both in vitro and in vivo. Cells exposed to multi-dose irradiation and pretreated with 5-ALA in vitro had a significantly lower surviving fraction compared with cells without 5-ALA pretreatment. Following multi-dose irradiation in vivo, the volume of the subcutaneous tumors treated with 5-ALA was significantly lower compared with that of tumors without treatment. These results suggest that radiotherapy with 5-ALA may enhance the therapeutic effect in colon cancer.

Keywords: 5-aminolevulinic acid; colorectal cancer; protoporphyrin IX; radiosensitivity; radiosensitizing effect; radiotherapy.

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Figures

Figure 1.
Figure 1.
Surviving fraction after single-dose and multi-dose radiations in vitro. (A) In the single-dose radiation experiment, the RT+5-ALA group tended to have a lower surviving fraction compared with that in the RT group; however, there was no significant difference. (B) In the multi-dose radiation experiment, the RT+5-ALA group had a significantly lower surviving fraction compared with that in the RT group. Data are presented as the mean ± standard deviation (n=3). *P<0.05. RT, radiotherapy; 5-ALA, 5-aminolevulinic acid.
Figure 2.
Figure 2.
Tumor size ratio after single-dose and multi-dose radiations in vivo. (A) In the single-dose radiation experiment, the tumor size of the RT+5-ALA group (n=6) was larger compared with that of the RT group (n=2) at day 21. (B) In the multi-dose irradiation experiment, significant differences were identified between the control group (n=3) and RT+5-ALA group (n=5) at day 8 (P=0.0290), 10 (P=0.0365), 13 (P=0.0057), 15 (P=0.0088), 17 (P=0.0163) and 20 (P=0.0178). Data are presented as the mean ± standard deviation. *P<0.05 vs. control. RT, radiotherapy; 5-ALA, 5-aminolevulinic acid.
Figure 3.
Figure 3.
Tumor weights following treatment. No significant difference was identified in the tumor weights of the RT+5-ALA (n=5) and RT groups (n=5); however, the tumor weight in the RT+5-ALA group was markedly lower compared with that in the RT group (P=0.45). Data are presented as the mean ± standard deviation. RT, radiotherapy; 5-ALA, 5-aminolevulinic acid.
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