过表达BTG2增强人肺腺癌细胞的辐射敏感性

在肺癌类型中,肺腺癌占大多数,其总体生存率差,BTG2是抗增殖基因家族的一员,属于BTG/TOB家族。许多研究表明,B细胞易位基因2(BTG2)多种类型的肿瘤中存在异常表达,但其在肺腺癌放疗敏感性中发挥的调控作用尚不明确。本研究通过肺腺癌组织样本及在线数据库,探究BTG2在肺腺癌患者中的表达水平及其表达与临床预后之间的相关性,结果提示在具有放疗抗性的肺腺癌患者中,BTG2的表达水平显著降低,且在肺腺癌细胞系中,BTG2能对放疗产生响应,其在肺腺癌患者中的低表达状态与不良的预后相关(P＜0.05);在人肺腺癌A549和H1299细胞系中转染过表达BTG2(OE-BTG2)慢病毒,通过克隆形成检测过表达BTG2对肺腺癌细胞系的辐射敏感性的影响,实验证实过表达BTG2可显著增强A549和H1299细胞系的辐射敏感性(P＜0.05);并进一步通过WB、免疫组化检测BTG2及凋亡相关蛋白BAX的表达水平,结果证实:过表达BTG2可显著增加A549和H1299细胞辐射后的凋亡水平。最后通过裸鼠成瘤试验检测BTG2在活体中对肺腺癌辐射敏感性的影响,结果提示:在动物实验中,过表达BTG2可显著增强肺腺癌的辐射敏感性(P＜0.05)及增加辐射后BAX的表达水平。综上所述,BTG2在肺腺癌组织中处于低表达状态,并且与不良的临床预后紧密相关,过表达BTG2可促进凋亡过程,增加人肺腺癌细胞系的辐射敏感性,能为克服肺腺癌的辐射抗性提供新的靶点。

The Expression of BTG2 and Its Regulatory Effect on Radiosensitivity of Lung Adenocarcinoma

Among the types of lung cancer, lung adenocarcinoma accounts for the majority, and its overall survival rate is poor. B-cell translocation gene 2 (BTG2) is a member of the antiproliferative gene family, belonging to the BTG/TOB family. Many studies have shown that BTG2 was abnormally expressed in many types of tumors, but its regulatory role in the radiosensitivity of lung adenocarcinoma remained unclear. In this study, we explored the expression level of BTG2 in patients with lung adenocarcinoma and its correlation with clinical prognosis through online database and tissue samples of lung adenocarcinoma patient. The results indicated that the expression level of BTG2 decreased significantly in lung adenocarcinoma patient with radiation resistance. Bioinformatics analysis confirmed that BTG2 could respond to radiotherapy in lung adenocarcinoma cell lines, and its low expression in lung adenocarcinoma patients was associated with poor prognosis (P < 0.05). The lentivirus overexpressing BTG2 (OE-BTG2) was transfected into human lung adenocarcinoma cell lines to increase the expression level of BTG2 including A549 and H1299. And the effect of BTG2 overexpression on the radiosensitivity of lung adenocarcinoma cell lines was detected by clone formation assay. Clone formation experiment confirmed that overexpression of BTG2 could significantly enhance the radiosensitivity of A549 and H1299 cell lines (P < 0.05). The expression levels of BTG2 and apoptosis related protein-Bax were detected by Western blotting (WB) and immunohistochemistry (IHC). The effect of BTG2 on radiation sensitivity of lung adenocarcinoma was further detected via nude mouse in vivo. WB experiment confirmed that BTG2 upregulation could significantly increase the apoptosis level of A549 and H1299 cells after radiation. Moreover, BTG2 overexpression can markedly enhance the radiosensitivity of lung adenocarcinoma (P < 0.05) and increase the protein level of Bax after radiation in vivo. In conclusion, BTG2 had low expression in lung adenocarcinoma patients and its low expression level was closely related to the poor clinical prognosis. Overexpression of BTG2 can increase the radiosensitivity of lung adenocarcinoma cell lines and promote the process of apoptosis after radiation, indicating a new target for overcoming the radiation resistance of lung adenocarcinoma.