Presentation miRNA 200c Sensitize Pancreatic Cancer Stem Cells to Carbon Ion Beam Irradiation

崔, 星  ,  鈴木, 雅雄

MicroRNAs (miRNAs), one of the most important non-coding RNAs, generally bind to a specific target messenger RNA with a complementary sequence to induce cleavage, or degradation or block translation. Recently, some miRNAs were found to be involved in regulating cancer stem cell (CSC) properties. Because CSCs have been shown to be resistant to conventional chemotherapy and radiation therapy, and heavy ion radiotherapy is effective in treating those of radioresistant human cancers, here we plan to explore new molecular mechanisms produced by carbon ion beam in combination with miRNA200c mimic from the point of view of targeting CSCs in vitro. Human pancreatic CSCs sorted from PK45, PANC1 cells were treated with carbon ion beam, X-ray irradiation alone or in combination with miRNA200c mimic, and then cell viability assay, colony, spheroid formation ability assay, and real time PCR analysis of apoptosis and autophagy related gene expression were performed. Carbon ion beam combined with miRNA200c mimic significantly decreased CSC viability. The colony, spheroid formation assays confirmed that subpopulation of CD44+/ESA+ exactly have CSC properties compared to CD44-/ESA- cells in pancreatic cancer cells. Real time PCR analysis showed that apoptosis- and autophagy-related gene expression was significantly induced after carbon ion beam combined with miRNA200c mimic compared to carbon ion alone or X-ray combined with miRNA200c mimic in pancreatic cancer cells. Taken together, because the carbon ion beams have a well-defined range with well-localized energy called “spread out bragg peak (SOBP)”, and release enormous energy at the end of their range, carbon ion beams therefore induce more irreparable DNA damage and kill more radioresistant CSCs than photon beams, and combination with a miRNA200c mimic further enhances those of actions based on the present data. Altogether, carbon ion beam has superior potential to kill pancreatic CSCs when combined with miRNA200c mimic compared to carbon ion beam alone.
43th Naito Conference

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