The Expression of BTG2 and Its Regulatory Effect on Radiosensitivity of Lung Adenocarcinoma / 中国生物化学与分子生物学报

ABSTRACT

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.