Effects of pheophorbide a-mediated photodynamic therapy on proliferation and metastasis of human prostate cancer cells

OBJECTIVE: To observe the effects of pheophorbide a-mediated photodynamic therapy (Pa-PDT) on the in vitro proliferation, apoptosis, invasion and metastasis of human prostate cancer PC-3 cells and to investigate its possible mechanism.

MATERIALS AND METHODS: Pa-PDT in gradient concentrations (0 μM, 0.25 μM, 0.5 μM, 1 μM, 2 μM, and 4 μM) were used to act on PC-3 cells; the cell proliferation in each group was detected via methyl thiazolyl tetrazolium (MTT) assay and clone formation assay, and the cell apoptosis was detected via Hochst33258 staining and Annexin V/propidium iodide (PI) double labeling. Moreover, the effects of Pa-PDT on invasion and proliferation of PC-3 cells were observed via wound healing assay and transwell chamber assay. Finally, the expressions of apoptosis-related proteins, epithelial-mesenchymal transition (EMT)-related proteins and matrix metalloproteinases (MMPs) in each group were detected after treatment by Western blotting.

RESULTS: MTT and clone formation assays showed that Pa-PDT could inhibit the proliferation of PC-3 cells in a dose-dependent manner. The results of apoptosis assay revealed that Pa-PDT could significantly promote the apoptosis of PC-3 cells, obviously up-regulate the expressions of pro-apoptotic proteins, such as B-cell lymphoma-2-associated X protein (BAX), Caspase-3 and poly adenosine diphosphate-ribose polymerase (PARP), and inhibit the expression of Bcl-2. Besides, the wound healing assay and Transwell chamber assay showed that Pa-PDT could inhibit the invasion and metastasis capacities of PC-3 cells, whose relevant mechanisms were related to the fact that Pa-PDT inhibited the EMT process and down-regulated the expressions of MMPs in PC-3 cells.

CONCLUSIONS: Pa-PDT can inhibit the proliferation and promote the apoptosis of PC-3 cells. Moreover, it can also inhibit the invasion and metastasis capacities of PC-3 cells via inhibiting the EMT process and down-regulating the expressions of MMPs.

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