Department of Surgical Oncology, Osaka City University Graduate School of Medicine, Abeno-ku, Osaka, Japan.
Anticancer Res. 2011 Oct;31(10):3369-75.
The aim of this study was to examine the effects of hypoxia on radiosensitivity and to analyze the mechanisms responsible for radiation resistance in gastric and esophageal cancer.
A gastric cancer cell line, OCUM-12, and an esophageal cancer cell line, TE-6, were used. The effects of hypoxia with irradiation on the growth-activity, cell cycle distribution, and gene expression were examined.
Both acute and chronic hypoxia decreased radiosensitivity of cancer cells. The radiosensitivity of chronic hypoxic cells was significantly enhanced by reoxygenation. Acute and chronic all hypoxia reduced the percentage of cells in the G(2)/M and S phases, respectively. In acute hypoxia, the mRNA expression of BRCA1 and BRCA2 was reduced in cancer cells. Reoxygenation increased the expression of BRCA1 and BRCA2.
Hypoxia is associated with radiation resistance. Therefore, reoxygenation may enhance the radiosensitivity of hypoxic cells. BRCA1 and BRCA2 may be associated with factors for radiation resistance by regulation of cell cycle progression.
本研究旨在探讨缺氧对放射敏感性的影响,并分析导致胃癌和食管癌辐射抗性的机制。
使用胃癌细胞系 OCUM-12 和食管癌细胞系 TE-6。检测缺氧与照射对细胞生长活性、细胞周期分布和基因表达的影响。
急性和慢性缺氧均降低了癌细胞的放射敏感性。复氧显著增强了慢性缺氧细胞的放射敏感性。急性和慢性缺氧分别减少了 G(2)/M 和 S 期细胞的百分比。在急性缺氧中,癌细胞中 BRCA1 和 BRCA2 的 mRNA 表达减少。复氧增加了 BRCA1 和 BRCA2 的表达。
缺氧与辐射抗性有关。因此,复氧可能会增强缺氧细胞的放射敏感性。BRCA1 和 BRCA2 可能通过调节细胞周期进程与辐射抗性的相关因素有关。