Upregulation of BTG1 enhances the radiation sensitivity of human breast cancer in vitro and in vivo.
Upregulation of BTG1 enhances the radiation sensitivity of human breast cancer in vitro and in vivo.
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DOI：
10.3892/or.2015.4311
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发表时间：
2015-12
期刊：
影响因子：
4.2
通讯作者：
Ran Zhu;Wei Li;Yan Xu;Jian-mei Wan;Zengli Zhang
中科院分区：
文献类型：
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作者：
Ran Zhu;Wei Li;Yan Xu;Jian-mei Wan;Zengli Zhang
以X射线为基础的放射治疗是乳腺癌患者最有效的治疗策略之一。然而，辐射抗性和副作用仍然是最具挑战性的问题。B-cell translocation gene 1（BTG 1）是BTG/Tob家族的成员，其抑制癌症生长并促进细胞凋亡。因此，我们假设BTG 1在乳腺癌细胞的放射敏感性中起重要作用。在本研究中，乳腺癌细胞系，稳定过表达BTG 1被用来研究BTG 1对细胞的放射敏感性在体外的影响。我们发现BTG 1的过表达增强了p53突变型乳腺癌MDA-MB-231细胞和p53野生型乳腺癌MCF-7细胞的放射敏感性。我们还发现BTG 1的过表达沿着照射诱导细胞周期G2/M期阻滞，促进活性氧（ROS）的形成，增加染色体畸变率，增加细胞凋亡。进一步的研究表明，BTG 1过表达沿着辐射参与了PI 3 K/Akt信号通路的抑制。重要的是，BTG 1在体外促进乳腺癌细胞电离辐射敏感性的发现在动物模型中得到了证实。综上所述，我们的数据表明，BTG 1过表达结合放射治疗通过调节细胞周期和乳腺癌相关信号通路增加乳腺癌治疗的疗效。
X-ray-based radiotherapy is one of the most effective therapeutic strategies for breast cancer patients. However, radioresistance and side-effects continue to be the most challenging issues. B-cell translocation gene 1 (BTG1) is a member of the BTG/Tob family, which inhibits cancer growth and promotes apoptosis. We, therefore, hypothesized that BTG1 plays an important role in the radiosensitivity of breast cancer cells. In the present study, breast cancer cell lines that stably overexpressed BTG1 were used to investigate the effects of BTG1 on cell radiosensitivity in vitro. We found that overexpression of BTG1 enhanced the radiosensitivity both of p53-mutant breast cancer MDA-MB-231 cells and p53 wild-type breast cancer MCF-7 cells. We also found that overexpression of BTG1 along with irradiation induced cell cycle G2/M phase arrest, promoted the formation of reactive oxygen species (ROS), increased the rate of chromosomal aberrations and increased cell apoptosis. Further investigation indicated that BTG1 overexpression along with irradiation was involved in inhibition of the PI3K/Akt signaling pathway. Importantly, the finding that BTG1 promoted ionizing radiosensitivity of breast cancer cells in vitro was confirmed in an animal model. Taken together, our data suggest that BTG1 overexpression combined with radiation therapy increases the therapeutic efficacy of breast cancer treatment via regulation of the cell cycle and apoptosis-related signaling pathways.