Purpose: The study investigated the molecular mechanisms that killed pancreatic cancer cells, including cancer stem cells (CSCs), by carbon ion beam irradiation alone or in combination with miRNA-200c under in vitro and in vivo conditions.
Methods: Human pancreatic cancer (PC) cells, PANC1 and PK45, were treated with carbon-ion beam irradiation alone or in combination with microRNA-200c (miR-200c) mimic. Cell viability assay, colony and spheroid formation assay, quantitative real-time PCR analysis of apoptosis-, autophagy-, and angiogenesis-related gene expression, xenograft tumor control and histopathological analyses were performed.
Results: The cell viability assay showed that transfection of the miRNA-200c (10 nM) mimic into pancreatic CSC (CD44+/ESA+) and non-CSC (CD44-/ESA-) significantly suppressed proliferation of both types of cell populations described above. Combining carbon-ion beam irradiation with the miRNA-200c mimic significantly reduced the colony as well as spheroid formation abilities compared to that observed with the treatment of carbon-ion beam alone or X-ray irradiation combined with the miRNA-200c mimic. Moreover, the combination of carbon ion beam irradiation and miRNA-200c mimic increased the expression of apoptosis-related gene BAX, autophagy-related genes Beclin-1 and p62, addition of gemcitabine (GEM) further enhanced the expression of these genes. In vivo data showed that carbon-ion beam irradiation in combination with the miRNA-200c mimic effectively suppressed xenograft tumor growth and significantly induced tumor necrosis and cavitation.
Conclusion: The combination of miRNA-200c mimic and carbon ion beam irradiation may be powerful radiotherapy that significantly kills pancreatic cancer cells containing CSCs and enhances the effect of carbon-ion beam irradiation compared to carbon-ion beam irradiation alone.

Keywords: pancreatic cancer stem cell, miR-200c, carbon-ion beam

中文翻译：

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碳离子束照射和 miR-200c Mimic 在体外和体内条件下有效根除胰腺癌干细胞

目的：该研究调查了在体外和体内条件下单独通过碳离子束照射或与 miRNA-200c 联合杀死胰腺癌细胞（包括癌症干细胞 (CSCs)）的分子机制。
方法：人胰腺癌 (PC) 细胞 PANC1 和 PK45 单独用碳离子束照射或与 microRNA-200c (miR-200c) 模拟物联合处理。进行了细胞活力测定、集落和球体形成测定、凋亡、自噬和血管生成相关基因表达的定量实时 PCR 分析、异种移植肿瘤控制和组织病理学分析。
结果：细胞活力测定表明，将 miRNA-200c (10 nM) 模拟物转染到胰腺 CSC (CD44+/ESA+) 和非 CSC (CD44-/ESA-) 中显着抑制了上述两种细胞群的增殖。与单独使用碳离子束或 X 射线照射与 miRNA-200c 模拟物相结合的情况相比，碳离子束照射与 miRNA-200c 模拟物相结合显着降低了菌落和球状体形成能力。此外，碳离子束照射和 miRNA-200c 模拟物的组合增加了细胞凋亡相关基因 BAX、自噬相关基因Beclin-1和p62的表达。, 添加吉西他滨 (GEM) 进一步增强了这些基因的表达。体内数据显示，碳离子束照射与 miRNA-200c 模拟物相结合可有效抑制异种移植肿瘤的生长，并显着诱导肿瘤坏死和空洞。
结论： miRNA-200c模拟物与碳离子束照射相结合可能是一种强效放疗，与单独的碳离子束照射相比，碳离子束照射可显着杀死含有CSCs的胰腺癌细胞，并增强了碳离子束照射的效果。

关键词：胰腺癌干细胞，miR-200c，碳离子束