Hematoporphyrin monomethyl ether mediated photodynamic therapy inhibits oral squamous cell carcinoma by regulating the P53-miR-21-PDCD4 axis via singlet oxygen.

Abstract

The objective of this study was to determine the mechanism and effect of hematoporphyrin monomethyl ether mediated photodynamic therapy (HMME-PDT) on oral squamous cell carcinoma (OSCC). Human OSCC CAL-27 cells were randomly divided into four groups: control group, HMME group, laser group, and HMME-PDT group. Cell viability was detected by the CCK-8 method. Cell cycle distribution was evaluated by flow cytometry. GEO database was used to screen differentially expressed microRNAs (DEMs), and TCGA database was performed to verify DEM expression in OSCC and normal tissues. The effects of HMME-PDT on DEM expression were assayed by real-time PCR, and the expressions of miRNAs target genes were measured by western blot. Fluorescence probes were used to determine the production of singlet oxygen (1O2). Compared with the other three groups, HMME-PDT dramatically inhibited CAL-27 cell proliferation and induced G0/G1 cycle arrest. The expressions of miR-21 and miR-155 were significantly upregulated in OSCC. HMME-PDT downregulated the expression of miR-21 but had no obvious effect on miR-155. HMME-PDT remarkably upregulated the levels of P53 and miR-21 target proteins, such as PDCD4, RECK, and SPRY2. 1O2 was generated during HMME-PDT, and inhibition of 1O2 production could reverse the regulation of HMME-PDT on P53, miR-21, and its target proteins, thus restoring cell viability. HMME-PDT can significantly inhibit the growth of OSCC cells, and the mechanism of this effect is related to the regulation of the P53-miR-21-PDCD4 axis via 1O2 induced by HMME-PDT.

• Authors: Peisong Meng, Yi Sun, Enze Li, Yunqing Liu, Cuiping Wang, Liping Song
• Journal: Lasers in medical science (Lasers Med Sci) Vol. 37 Issue 6 Pg. 1-9 (Aug 2022) ISSN: 1435-604X [Electronic] England
• PMID: 35260928 (Publication Type: Journal Article)
• Copyright: © 2022. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.

Chemical References

• Apoptosis Regulatory Proteins
• GPI-Linked Proteins
• Hematoporphyrins
• Intracellular Signaling Peptides and Proteins
• MIRN21 microRNA, human
• Membrane Proteins
• MicroRNAs
• PDCD4 protein, human
• Photosensitizing Agents
• RECK protein, human
• RNA-Binding Proteins
• SPRY2 protein, human
• Tumor Suppressor Protein p53
• hematoporphyrin monomethyl ether
• Singlet Oxygen

Topics

• Apoptosis
• Apoptosis Regulatory Proteins
• Carcinoma, Squamous Cell (drug therapy, genetics)
• Cell Line, Tumor
• GPI-Linked Proteins
• Head and Neck Neoplasms
• Hematoporphyrins (pharmacology)
• Humans
• Intracellular Signaling Peptides and Proteins
• Membrane Proteins (metabolism)
• MicroRNAs (genetics)
• Mouth Neoplasms (drug therapy, genetics)
• Photochemotherapy (methods)
• Photosensitizing Agents (pharmacology, therapeutic use)
• RNA-Binding Proteins
• Singlet Oxygen
• Squamous Cell Carcinoma of Head and Neck (drug therapy)
• Tumor Suppressor Protein p53 (genetics)