Department of Radiation Oncology, Affiliated Hospital of Jiangnan University, Wuxi, China.
Department of Interventional Radiology, Affiliated Hospital of Jiangnan University, Wuxi, China.
Environ Toxicol. 2022 Jul;37(7):1711-1722. doi: 10.1002/tox.23519. Epub 2022 Mar 14.
Non-small cell lung cancer is a common respiratory tumor. The mortality rate of lung cancer patients has continued to rise in recent years. Several studies revealed that the expression of melanoma antigen 6 (MAGE-A6) promoted the development of multiple types of cancer. In addition, the suppression of AMPK pathway could restrict the radiosensitization of prostate cancer cells. Inhibition of MAGE-A6 activated the AMPK pathway in colorectal cancer cells. However, whether the MAGE-A6 could regulate the radiosensitivity of non-small cell lung cancer cells by regulating of the AMPK pathway is unclear. In this study, we established the MAGE-A6 knockdown in A549 and H1299 cells. Next, the apoptosis and proliferation of these cells were detected by the flow cytometry analysis and colony formation assay after the irradiation, respectively. Then, the expression of p-AMPKα1 and p-S6K1 in these cells was explored by the western blotting. After that, we inhibited the expression of AMPKα1 in MAGE-A6 knockdown cells. The proliferation and apoptosis of these cells were detected with colony formation assay and flow cytometry analysis. Finally, the tumor formation of these cells was detected in nude mice. Our results showed that inhibition of MAGE-A6 suppressed the proliferation and aggravated the apoptosis of A549 and H1299 cells after the irradiation. Knockdown of MAGE-A6 activated the expression of p-AMPKα1 and repressed the expression of p-S6K1 in these cells. Suppression of AMPKα1 in MAGE-A6 knockdown cells abolished these effects. Knockdown of MAGE-A6 also enhanced the radiosensitivity of these cells in vivo. These results suggested that inhibition of MAGE-A6 promoted the radiosensitivity of non-small cell lung cancer cells by activating AMPK pathway. Therefore, MAGE-6 has the potential to be explored as the therapeutic target for the treatment of non-small cell lung cancer in clinical.
非小细胞肺癌是一种常见的呼吸道肿瘤。近年来，肺癌患者的死亡率持续上升。几项研究表明，黑色素瘤抗原 6（MAGE-A6）的表达促进了多种类型癌症的发展。此外，AMPK 通路的抑制可以限制前列腺癌细胞的放射增敏作用。抑制 MAGE-A6 可激活结直肠癌细胞中的 AMPK 通路。然而，MAGE-A6 是否可以通过调节 AMPK 通路来调节非小细胞肺癌细胞的放射敏感性尚不清楚。在本研究中，我们在 A549 和 H1299 细胞中建立了 MAGE-A6 敲低。接下来，通过流式细胞术分析分别检测照射后这些细胞的凋亡和增殖，通过 Western blot 检测这些细胞中 p-AMPKα1 和 p-S6K1 的表达。然后，我们抑制了 MAGE-A6 敲低细胞中 AMPKα1 的表达。通过集落形成实验和流式细胞术分析检测这些细胞的增殖和凋亡。最后，在裸鼠中检测这些细胞的肿瘤形成。我们的结果表明，抑制 MAGE-A6 抑制了 A549 和 H1299 细胞在照射后的增殖并加重了其凋亡。MAGE-A6 的敲低激活了这些细胞中 p-AMPKα1 的表达并抑制了 p-S6K1 的表达。在 MAGE-A6 敲低细胞中抑制 AMPKα1 消除了这些作用。MAGE-A6 的敲低也增强了这些细胞在体内的放射敏感性。这些结果表明，抑制 MAGE-A6 通过激活 AMPK 通路促进了非小细胞肺癌细胞的放射敏感性。因此，MAGE-6 有可能作为临床治疗非小细胞肺癌的治疗靶点进行探索。
