NDLI: Hypoxia-inducible factor-1/spl alpha/ (HIF-1/spl alpha/) and photodynamic therapy

Content Provider	IEEE Xplore Digital Library
Author	Lin-Hung Wei Chia-Hung Chou Jen-Liang Su
Copyright Year	2004
Description	Author affiliation: Dept. of Oncology, Nat. Taiwan Univ., Taipei, Taiwan (Lin-Hung Wei)
Abstract	Summary form only given. Photodynamic therapy (PDT) is a promising treatment modality that is being tested in the clinic for use in oncology. PDT requires three elements: light, a photosensitizer and oxygen. PDT-mediated oxidative stress elicits direct tumor cell damage and microvascular injury within exposed tumor. Microvasculature damage following PDT leads to a significant decrease in blood flow as well as severe and persistent tumor tissue hypoxia. Subsequently, tissue hypoxia can induce a plethora of molecular and physiological responses, including an adaptive response associated with gene activation. A primary step in hypoxia-mediated gene activation is the formation of the hypoxia-inducible factor (HIF-1) transcription factor complex. Hypoxia induces the stabilization of the HIF-1/spl alpha/, which in turn allows for the formation of the transcriptionally active protein complex. Up to date, the HIF-1-responsive genes that can modulate the PDT response have not been well identified. In the current study, we employed 5-aminolevulinic acid as a photosensitizer, 630 nm wavelength light-emitting diode (LED) manufactured by the Industrial Technology Research Institute as a light source. The experimental results demonstrated that cancer cells are more resistant to PDT under hypoxic status. PDT can transcriptionally induce or enhance HIF-1/spl alpha/ expression in different cervical cancer cell lines (SiHa, HeLa, Caski, C33A, HT-3), immortalized cervical epithelium cell line 183 A, and human umbilical vein endothelial cells (HUVECs). Pharmacological and genetic inhibition assays revealed that PI3K/Akt signaling critically involves in the activation of HIF-1/spl alpha/ by PDT in SiHa cells. When SiHa cells was treated with antisense HIF-1/spl alpha/ (20/spl mu/M), PDT activated HIF-1/spl alpha/ protein expression was markedly inhibited, and subsequently sensitized SiHa cells to PDT. Currently, pharmaceutical companies actively develop novel compounds targeting HIF-1/spl alpha/ as a promising cancer therapy. The results of this study will, therefore, provide important information to improve the therapeutic efficacy of PDT and have great clinical applicable potential.
File Size	59882
File Format	PDF
ISBN	0780386760
DOI	10.1109/APBP.2004.1412292
Language	English
Publisher	Institute of Electrical and Electronics Engineers, Inc. (IEEE)
Publisher Date	2004-12-14
Publisher Place	Taiwan
Access Restriction	Subscribed
Rights Holder	Institute of Electrical and Electronics Engineers, Inc. (IEEE)
Subject Keyword	Proteins Medical treatment Light emitting diodes Oncology Neoplasms Stress Injuries Cancer Testing Tumors
Content Type	Text
Resource Type	Article

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