Abstract
Photodynamic therapy (PDT) is a novel and promising antitumor treatment. Phthalocyanine-mediated PDT has shown antitumor activity in some tumor cells, but the effect of new hydrophilic/lipophilic tetra-α-(4-carboxyphenoxy)phthalocyanine zinc (TαPcZn)-mediated PDT (TαPcZn-PDT) on human hepatocellular carcinoma Bel-7402 cells and underlying mechanisms have not been clarified. In the present study, therefore, the ultraviolet-visible (UV-vis) absorption spectrum and cellular localization of TαPcZn, and effect of TαPcZn-PDT on the proliferation, apoptosis, cell cycle, Bcl-2 and Fas in Bel-7402 cells were investigated by spectrophotometry, inverted microscope, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay, electron microscopy, annexinV-FITC/propidium iodide double staining, DNA content and immunoblot assay, respectively. We found that an intense absorption in UV-vis absorption spectrum of TαPcZn was in the red visible region at 650–680 nm, where light penetration in tissue is efficient, that green TαPcZn localized to both plasma membrane and nuclear membrane of Bel-7402 cells, signifying that there was a selective uptake of TαPcZn in Bel-7402 cells and TαPcZn-PDT would be expected to directly damage DNA, and that TαPcZn-PDT significantly resulted in the proliferation inhibition, apoptosis induction, S cell cycle arrest, and down-regulation of Bcl-2 and Fas. Taken together, we conclude that TαPcZn-PDT inhibits the proliferation of Bel-7402 cells by triggering apoptosis and arresting the cell cycle.
Highlights
IntroductionThe traditional therapies of surgery, chemotherapy and radiation therapy play an important role in the systemic treatment of hepatocellular carcinoma
Hepatocellular carcinoma is one of the most common malignant tumors in the world
Based on an in vitro model, we found that tetra-α-(4-carboxyphenoxy)phthalocyanine zinc (TαPcZn)-Photodynamic therapy (PDT) inhibited proliferation and induced apoptosis in Bel-7402 cells, simultaneously arresting the cells at S phase with concomitant downregulation of Bcl-2 and Fas
Summary
The traditional therapies of surgery, chemotherapy and radiation therapy play an important role in the systemic treatment of hepatocellular carcinoma. It is very important to find an effective alternative treatment for hepatocellular carcinoma. Photodynamic therapy (PDT) is a novel and promising antitumor treatment in which photosensitizing drugs that are excited with an appropriate wavelength of light significantly result in photochemical destruction of tumors by yielding reactive oxygen species (ROS), such as singlet oxygen and free radicals [1,2,3]. The outstanding advantage of PDT is that it destroys tumor through selective uptake of photosensitisers and precise application of the light with modern fiber-optic systems, and does not harm the normal surrounding tissues seriously
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