Effects of ALA-mediated photodynamic therapy on the invasiveness of human glioma cells

被引:27
|
作者
Hirschberg, Henry
Sun, Chung-Ho
Krasieva, Tatiana
Madsen, Steen J.
机构
[1] Univ Calif Irvine, Beckman Laser Inst & Med Clin, Irvine, CA 92612 USA
[2] Univ Nevada, Dept Hlth Phys, Las Vegas, NV 89154 USA
[3] Univ Oslo, Rikshosp, Dept Neurosurg, N-0027 Oslo, Norway
[4] Univ Nevada, UNLV Canc Res Ctr, Las Vegas, NV 89154 USA
关键词
ALA; brain tumor; glioma; invasive growth; photodynamic therapy;
D O I
10.1002/lsm.20445
中图分类号
R75 [皮肤病学与性病学];
学科分类号
100206 ;
摘要
Background and Objective: High-grade gliomas are characterized by rapid proliferation, angiogenesis, and invasive growth. Eradication or inhibition of infiltrating glioma cells poses a significant clinical challenge that is unlikely to be solved using conventional treatment regimens consisting of ionizing radiation and chemotherapeutic agents. In this study, we evaluated the effects of 5-aminolevulinic acid (ALA)-mediated photodynamic therapy (PDT) on the invasiveness of human glioma cells migrating from implanted multicell human tumor spheroids. Study Design/Materials and Methods: Tumor spheroids, derived from the human glioma cell line ACBT, were implanted into a gel matrix of collagen type I. Twenty-four hours following implantation there was a significant invasion into the surrounding gel by individual tumor cells to an average distance of 400 mu m. The cultures were incubated in ALA for 4 hours and then exposed to 635 nm laser light in a titration of fluence level, fluence rate, and drug concentration. Results: ALA-PDT at a light fluence of 6 J/cm(2) was sufficient to inhibit gloma cell migration distance by 80-90% compared to control cultures, but did not prevent spheroid growth nor was it cytotoxic to the migrating cells. The viability of the migrating cells both in control and PDT-treated cultures receiving 6 J/cm(2) was high, 85 and 65%, respectively. ALA-PDT at fluences of 25 J/cm(2) was clearly cytotoxic for both the infiltrating cells as well as the spheroids. Low fluence rates were more effective at inhibiting tumor cell infiltration than higher ones for a given total fluence. Conclusion: Measurement of cell survival, and results from cultures with blocked cell proliferation, indicated a direct migratory inhibition effect on the invading cells rather than cytotoxicity as the most likely mechanism for the inhibition of invasiveness observed following ALA-mediated PDT.
引用
收藏
页码:939 / 945
页数:7
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