肾癌细胞中参与舒尼替尼耐药的微小RNA的鉴定
Identification of MicroRNAs Involved in Resistance to Sunitinib in Renal Cell Carcinoma Cells.
作者信息
Yamaguchi Noriya, Osaki Mitsuhiko, Onuma Kunishige, Yumioka Tetsuya, Iwamoto Hideto, Sejima Takehiro, Kugoh Hiroyuki, Takenaka Atsushi, Okada Futoshi
机构信息
Division of Pathological Biochemistry, Institute of Regenerative Medicine and Biofunction, Graduate School of Medical Science, Tottori University, Tottori, Japan.
Department of Surgery, Division of Urology, Faculty of Medicine, Institute of Regenerative Medicine and Biofunction, Graduate School of Medical Science, Tottori University, Tottori, Japan.
出版信息
Anticancer Res. 2017 Jun;37(6):2985-2992. doi: 10.21873/anticanres.11652.
AIM
To generate sunitinib-resistant renal cell carcinoma (RCC) cell lines and identify miRNAs contributing to sunitinib resistance.
MATERIALS AND METHODS
Two RCC cell lines, ACHN and RCC23, were cultured by continuous treatment with sunitinib for 3 months, with doses gradually increasing up to the 50% inhibitory concentration for each cell line. We performed microarray and quantitative real-time polymerase chain reaction analyses of sunitinib-resistant ACHN (SR-ACHN) and RCC23 (SR-RCC23) cells, as well of as sunitinib-sensitive ACHN and RCC23 cells.
RESULTS
SR-ACHN and SR-RCC23 cells exhibited significantly higher resistance to sunitinib treatment compared to sunitinib-sensitive cells. SR-ACHN and SR-RCC23 cells were hypertrophic and contained granules in the cytoplasm. When SR-ACHN and SR-RCC23 cells were compared to ACHN and RCC23 cells, expression of miR-575, miR-642b-3p, and miR-4430 was significantly increased, while that of miR-18a-5p, miR-29b-1-5p, miR-431-3p, and miR-4521 was significantly decreased.
CONCLUSION
These miRNAs may contribute to sunitinib resistance in humans.
目的
建立舒尼替尼耐药的肾细胞癌（RCC）细胞系，并鉴定与舒尼替尼耐药相关的微小RNA（miRNA）。
材料与方法
对两种肾癌细胞系ACHN和RCC23进行连续3个月的舒尼替尼处理，剂量逐渐增加至每种细胞系的50%抑制浓度。我们对舒尼替尼耐药的ACHN（SR-ACHN）和RCC23（SR-RCC23）细胞以及舒尼替尼敏感的ACHN和RCC23细胞进行了微阵列和定量实时聚合酶链反应分析。
结果
与舒尼替尼敏感细胞相比，SR-ACHN和SR-RCC23细胞对舒尼替尼治疗表现出显著更高的耐药性。SR-ACHN和SR-RCC23细胞肥大，细胞质中含有颗粒。当将SR-ACHN和SR-RCC23细胞与ACHN和RCC23细胞进行比较时，miR-575、miR-642b-3p和miR-4430的表达显著增加，而miR-18a-5p、miR-29b-1-5p、miR-431-3p和miR-4521的表达显著降低。
结论
这些miRNA可能与人类舒尼替尼耐药有关。
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