Researchers from China demonstrated that photodynamic therapy (PDT) inhibited proliferation and promoted apoptosis in cholangiocarcinoma cells, as published in Biochemical and Biophysical Research Communications.
The effects seemed to be partly mediated by the wingless-related integration site (Wnt) signaling. Mechanistically, the researchers showed that PDT decreased the expression of Wnt-7b, β-catenin, c-Myc, and cyclin D1 while increasing the expression of axin-2 in 2 perihilar cholangiocarcinoma cell lines.
In addition, they showed that PDT enhanced the expression of the tumor suppressor protein p53 and the microRNA (miR) miR-34a-5p. The treatment of p53-knockdown cells with PDT inhibited cell apoptosis.
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“As recently reported, p53 seems to exert a substantial effect on cell apoptosis due to porphyrin-mediated PDT via the direct interaction between p53 and drug, leading to its accumulation and induction of p53-dependent apoptosis away from light and under irradiation,” the researchers wrote.
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The effects of p53 knockdown in PDT-treated cholangiocarcinoma cells were restrained by the overexpression of miR-34a-5p. Hence, miR-34a-5p overexpression decreased cell viability while promoting apoptosis. As a consequence of miR-34a-5p downregulation, the expression of axin-2 decreased and the expression of β-catenin, c-Myc, and cyclin D1 increased.
By using specific tools to upregulate and downregulate the expression of miR-34a-5p, the researchers found that it also targeted Wnt-7b directly, and miR-34a-5p-mediated inhibition of Wnt-7b was dependent on protein argonaute-2.
The treatment of Wnt-7b-knockdown cells with PDT had opposite effects to those observed upon miR-34a-5p knockdown and was able to attenuate the impact of miR-34a-5p inhibition.
PDT takes advantage of the selective aggregation properties of photosensitizers to kill tumor cells. The PDT protocol selected for this study used 5-aminolevulinic acid, a photosensitizing precursor that has been applied to photodynamic diagnosis and PDT.
Reference
Han Y, Yang Y, Huang S, Yao L, Wu L. The miR-34a/WNT7B modulates the sensitivity of cholangiocarcinoma cells to p53-mediated photodynamic therapy toxicity. Biochem Biophys Res Commun. 2022;591(5):54-61. doi:10.1016/j.bbrc.2021.12.070
