Photodynamic therapy mediated by 5-aminolevulinic acid suppresses gliomas growth by decreasing the microvessels

Abstract

Although 5-aminolevulinic acid (5-ALA)-mediated photodynamic therapy (PDT) has been demonstrated to be a novel and effective therapeutic modality for some human malignancies, its effect and mechanism on glioma are still controversial. Previous studies have reported that 5-ALA-PDT induced necrosis of C6 rat glioma cells in vitro. The aim of this study was to further investigate the effect and mechanism of 5-ALA-PDT on C6 gliomas implanted in rats in vivo. Twenty-four rats bearing similar size of subcutaneously implanted C6 rat glioma were randomly divided into 3 groups: receiving 5-ALA-PDT (group A), laser irradiation (group B), and mock procedures but without any treatment (group C), respectively. The growth, histology, microvessel density (MVD), and apoptosis of the grafts in each group were determined after the treatments. As compared with groups B and C, the volume of tumor grafts was significantly reduced (P<0.05), MVD was significantly decreased (P<0.001), and the cellular necrosis was obviously increased in group A. There was no significant difference in apoptosis among the three groups. The in vivo studies confirmed that 5-ALA-PDT may be an effective treatment for gliomas by inhibiting the tumor growth. The mechanism underlying may involve increasing the cellular necrosis but not inducing the cellular apoptosis, which may result from the destruction of the tumor microvessels.

Keywords

glioma / photodynamic therapy / 5-aminolevulinic acid / necrosis / microvessel

References

[1] EdWZ. Neurosurgery: Intracranial tumor, 2004, Wuhan, Hubei Science and Technology Press, 397-400

[2] SathornsumeteeS, RichJN. New treatment strategies for malignant gliomas. Expert Rev Anticancer Ther, 2006, 6(7): 1087-1104 PMID: 16831080

[3] AokiT, HashimotoN, MatsutaniM. Management of glioblastoma. Expert Opinion Pharmacother, 2007, 8(18): 3133-3146

[4] TomankovaK, KolarovaH, KolarP, et al. . Study of cytotoxic effect of photodynamically and sonodynamically activated sensitizers in vitro. Toxicol In Vitro, 2009, 23(8): 1465-1471 PMID: 19595758

[5] LemanJA, MortonCA. Photodynamic therapy: applications in dermatology. Expert Opin Biol Ther, 2002, 2(1): 45-53 PMID: 11772339

[6] BarrH, KendallC, StoneN. Photodynamic therapy for esophageal cancer: a useful and realistic option. Technol Cancer Res Treat, 2003, 2(1): 65-76 PMID: 12625755

[7] McGillisST, FeinH. Topical treatment strategies for non-melanoma skin cancer and precursor lesions. Semin Cutan Med Surg, 2004, 23(3): 174-183 PMID: 15584683

[8] SvatekRS, KamatAM, DinneyCP. Novel therapeutics for patients with non-muscle-invasive bladder cancer. Expert Rev Anticancer Ther, 2009, 9(6): 807-813 PMID: 19496717

[9] PogueBW, Gibbs-StraussS, ValdesPA, et al. . Review of neurosurgical fluorescence imaging methodologies. IEEE J Sel Top Quantum Electron, 2010, 16(3): 493-505 PMCID: 2910912 PMID: 20671936

[10] RedmondRW, GamlinJN. A compilation of singlet oxygen yields from biologically relevant molecules. Photochem Photobiol, 1999, 70(4): 391-475 PMID: 10546544

[11] FotinosN, CampoMA, PopowyczF, et al. . 5-Aminolevulinic acid derivatives in photomedicine: Characteristics, application and perspectives. Photochem Photobiol, 2006, 82(4): 994-1015 PMID: 16542112

[12] LeggettCL, GorospeEC, MuradMH, et al. . Photodynamic therapy for unresectable cholangiocarcinoma: a comparative effectiveness systematic review and meta-analyses. Photodiagnosis Photodyn Ther, 2012, 9(3): 189-195 PMID: 22959798

[13] PengQ, NeslandJM. Effects of photodynamic therapy on tumor stroma. Ultrastruct Pathol, 2004, 28(5–6): 333-340 PMID: 15764581

[14] EljamelMS, GoodmanC, MoseleyH. ALA and Photofrin fluorescence-guided resection and repetitive PDT in glioblastoma multiforme: a single centre phase III randomised controlled trial. Lasers Med Sci, 2008, 23(4): 361-367 PMID: 17926079

[15] SteppH, BeckT, PongratzT, et al. . ALA and malignant glioma: fluorescence-guided resection and photodynamic treatment. J Environ Pathol Toxicol Oncol, 2007, 26(2): 157-164 PMID: 17725542

[16] CaoY, ZhangMZ, ZhaoJZ, et al. . Photodynamic diagnosis and fluorescence-guided resection of malignant gliomas: a report of 15 cases. Zhonghua Wai Ke Za Zhi (Chinese), 2005, 43(5): 334-338

[17] ZimmermannA, Ritsch-MarteM, KostronH. mTHPC-mediated photodynamic diagnosis of malignant brain tumors. Photochem Photobiol, 2001, 74(4): 611-616 PMID: 11683042

[18] HuangZ. A review of progress in clinical photodynamic therapy. Technol Cancer Res Treat, 2005, 4(3): 283-293 PMCID: 1317568 PMID: 15896084

[19] YooJ HK. New insights into the mechanisms for photodynamic therapy-induced cancer cell death. Int Rev Cell Mol Biol, 2012, 295: 139-174 PMID: 22449489

[20] KarmakarS, BanikNL, PatelSJ, et al. . 5-Aminolevulinic acid-based photodynamic therapy suppressed survival factors and activated proteases for apoptosis in human glioblastoma U87MG cells. Neurosci Lett, 2007, 415(3): 242-247 PMCID: 2533742 PMID: 17335970

[21] KamoshimaY, TerasakaS, IwasakiY. Photodynamic therapy mediated with 5-aminolevulinic acid for C6 glioma spheroids. Hokkaido Igaku Zasshi, 2008, 83(3): 167-173 PMID: 18546870

[22] KamoshimaY, TerasakaS, KurodaS, et al. . Morphological and histological changes of glioma cells immediately after 5-aminolevulinic acid mediated photodynamic therapy. Neurol Res, 2011, 33(7): 739-746 PMID: 21756554

[23] WeidnerN. Intratumor microvessel density as a prognostic factor in cancer. Am J Pathol, 1995, 147(1): 9-19 PMCID: 1869874 PMID: 7541613

[24] HuSS, ChengHB, ZhengYR, et al. . Effects of photodynamic therapy on the ultrastructure of glioma cells. Biomed Environ Sci, 2007, 20(4): 269-273 PMID: 17948759

[25] StummerW, TonnJC, MehdornHM, et al. . Counterbalancing risks and gains from extended resections in malignant glioma surgery: a supplemental analysis from the randomized 5-aminolevulinic acid glioma resection study. J Neurosurg, 2011, 114(3): 613-623 PMID: 20397896

[26] HirschbergH, SunCH, KrasievaT, et al. . Effects of ALA-mediated photodynamic therapy on the invasiveness of human glioma cells. Lasers Surg Med, 2006, 38(10): 939-945 PMID: 17163479

[27] HirschbergH, SpetalenS, CarperS, et al. . Minimally invasive photodynamic therapy (PDT) for ablation of experimental rat glioma. Minim Invasive Neurosurg, 2006, 49(3): 135-142 PMID: 16921452

[28] WuSM, RenQG, ZhouMO, et al. . Protoporphyrin IX production and its photodynamic effects on glioma cells, neuroblastoma cells and normal cerebellar granule cells in vitro with 5-aminolevulinic acid and its hexylester. Cancer Lett, 2003, 200(2): 123-131 PMID: 14568165

[29] OtakeM, NishiwakiM, KobayashiY, et al. . Selective accumulation of ALA-induced PpIX and photodynamic effect in chemically induced hepatocellular carcinoma. Br J Cancer, 2003, 89(4): 730-736 PMCID: 2376916 PMID: 12915887

[30] VrouenraetsMB, VisserGW, SnowGB, et al. . Basic principles, applications in oncology and improved selectivity of photodynamic therapy. Anticancer Res, 2003, 23(1B): 505-522 PMID: 12680139

[31] SilvaJN, FilipeP, MorliereP, et al. . Photodynamic therapies: principles and present medical applications. Biomed Mater Eng, 2006, 16(4Suppl): S147-S154 PMID: 16823106