Health Management Centre, Guangzhou First Municipal People's Hospital, Guangzhou Medical College, Guangzhou, Guangdong Province, China.
Cell Oncol (Dordr). 2011 Oct;34(5):451-6. doi: 10.1007/s13402-011-0020-1. Epub 2011 Apr 15.
Caner-initiating cells (CICs or cancer stem cells) have been shown both experimentally and clinically to be resistant to radiation. The mechanism underlying radioresistance remains unclear.
In the present study, we screened 51 genes which are potentially important in mediating radioresistance of breast CICs.
The expression of AKT1 and AKT2 at protein and mRNA levels was dramatically increased among the screened genes by 8 Gy radiation treatment in MCF-7 mammosphere cells (predominantly CD24(-/low)/CD44(+) CICs), but not in the bulk population of MCF-7 cells (predominantly CD24(+)/CD44(+)). Using apoptosis and clonogenic survival assays, we found pharmacological inhibition of AKT with selective inhibitors of AKT sensitized MCF-7 mammosphere cells, but not MCF-7 monolayer cells to radiation.
The present findings suggest that treatment with AKT inhibitors prior to ionizing radiation treatment may be a potential benefit to patients with breast cancer, in particular to eradiate breast CICs.
研究表明，癌起始细胞（CIC 或癌症干细胞）在实验和临床上均具有辐射抗性。其辐射抗性的机制尚不清楚。
本研究中，我们筛选了 51 个可能在调节乳腺癌 CIC 辐射抗性中起重要作用的基因。
在 MCF-7 乳腺球体细胞（主要为 CD24(-/low)/CD44(+) CIC）中，8Gy 辐射处理后，筛选出的基因中 AKT1 和 AKT2 的蛋白和 mRNA 水平均显著升高，但在 MCF-7 细胞的大部分群体（主要为 CD24(+)/CD44(+)）中则不然。通过凋亡和集落形成存活测定，我们发现 AKT 的选择性抑制剂可抑制 AKT，从而使 MCF-7 乳腺球体细胞而非 MCF-7 单层细胞对辐射敏感。
本研究结果表明，在进行电离辐射治疗之前使用 AKT 抑制剂治疗可能对乳腺癌患者有益，特别是可以消灭乳腺癌 CIC。
