摘要
目的探讨miR-29b与胃癌细胞顺铂耐受性之间的关系及其可能的调控机制。方法采用实时定量PCR(qRT-PCR)和Western blot法检测顺铂浓度梯度处理后胃癌细胞系中miR-29b及其靶基因的表达;CCK8法检测miR-29b敲低状态和过表达状态下胃癌细胞受顺铂处理后的增殖情况,评估miR-29b对胃癌细胞顺铂耐受性的影响。结果顺铂处理后miR-29b表达量显著上调,其靶基因AKT2表达下调。过表达miR-29b后胃癌细胞对顺铂抗性下降,干扰miR-29b表达后对顺铂的耐受性增强。Rescue实验结果显示,miR-29b通过AKT2促使胃癌细胞发挥对顺铂抗性的拮抗作用。miR-29家族另外两个成员miR-29a/c受顺铂诱导上调表达,但二者对胃癌细胞顺铂抗性的产生无显著作用。结论 miR-29b能够通过靶向抑制PI3K/Akt信号通路降低胃癌细胞对顺铂的耐受性。
Objective To investigate the regulatory effect of miR-29 b on gastric cells＇ resistance to cisplatin. Methods The expression of miR-29 b in gastric cancer cell line treated with cisplatin concentration gradient was detected using quantitative reverse-transcriptase polymerase chain reaction（ qRT-PCR） and Western blotting. CCK8 was used to measure the cell viability after cisplatin treatment in condition of miR-29 b knockdown and overexpression. Results The expression of miR-29 b was significantly upregualted by cisplatin treatment,while its target gene AKT2 was downregulated. The up-regulation of miR-29 b enhanced the sensitivity of gastric cancer cells to cisplatin,while the knock-down of miR-29 b enhanced the cisplatin resistance. Rescue experiments demonstrated that the miR-29 b might regulate cisplatin resistance of gastric cancer cell by targetingPI3 K / Akt pathway. The expressions of the other two members of miR-29 family,miR-29 a / c,were promoted by cisplatin treatment,but they had no significant effect on gastric cancer cell＇s resistance to cisplatin. Conclusion miR-29 b can enhance the sensitivity of S gastric cancer cell by directly targeting PI3 K / Akt pathway.
出处
《中国医学科学院学报》
CAS
CSCD
北大核心
2015年第5期514-519,共6页
Acta Academiae Medicinae Sinicae
基金
吴阶平基金会临床科研专项资助基金(32067501084)~~
