Abstract
The aim of this study is to investigate the antitumor effects and possible mechanisms of meta-tetrahydroxyphenylchlorin-mediated photodynamic therapy (m-THPC-PDT) on human primary (SW480) and metastatic (SW620) colon cancer cell lines. SW480 and SW620 cells were incubated with various concentrations of m-THPC, followed by photodynamic irradiation. Subcellular localization of m-THPC in cells was observed with confocal laser scanning microscopy (CLSM). Photocytotoxicity of m-THPC in the two cells was investigated by using MTT assay. The flow cytometry was employed to detect the cell apoptosis. The migration and long-term recovery ability were determined by scratch test and colony formation assay respectively. CLSM showed that m-THPC was mainly distributed within the endoplasmic reticulum (ER) and lysosome of SW480 cells and within the lysosome and mitochondria of SW620 cells. m-THPC-PDT induced a dose-dependent and light energy-dependent cytotoxicity in SW480 and SW620 cells. Apoptosis rate was approximately 65 and 25% in SW480 and SW620 respectively when the concentration of m-THPC increased to 11.76 μM. However, the rate of necrotic cells had no significant changes in two cell lines. The colony formation and migration ability of the two cell lines were decreased with m-THPC-PDT treatment in a dose-dependent manner. PDT with m-THPC not only could effectively inhibit cell proliferation and decrease migration ability and colony formation ability, but also could effectively kill SW480 and SW620 cells in a dose-dependent manner in vitro. These results suggest that m-THPC is a promising sensitizer that warrants further development and extensive studies towards clinical use of colorectal cancer.
Highlights
Colorectal cancer (CRC) is the third most common cancer in males and the second in females worldwide
Photodynamic therapy (PDT), a non- or minimally invasive therapeutic approach, is based on tumor-specific accumulation of a photosensitizer followed by its activation using an appropriate wavelength of laser light, which causes the generation of highly reactive oxygen species (ROS) within the tumor cells and induces tumor cell death [8, 14, 22, 23]
M-THPC, a second generation PS, is considered a potent PS activated at 652 nm, with a residual photosensitivity of only 2 weeks [29, 30]. m-THPC was used with curative purposes in the treatment of early-stage head and neck cancers and has been given approval for treatment of advanced head and neck cancers [15, 29]
Summary
Colorectal cancer (CRC) is the third most common cancer in males and the second in females worldwide. The survival rate of CRC patients correlates with tumor stage and the 5-year relative survival is approximately 65%. PDT is a Btrinity^ treatment modality composed of a Lasers Med Sci (2018) 33:1581–1590 photosensitizer (PS), light, and molecular oxygen [8, 9]. It is based on the administration of a non-toxic PS, a light sensitive compound with the preferential retention in neoplastic tissue, and subsequent illumination of the cancer lesion with light of appropriate wavelength [10]. The results show the effectiveness of mTHPC-PDT in killing human primary and metastatic colorectal cancer cell lines
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