Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Integration of Chinese and Western Medicine, Peking University Cancer Hospital & Institute, Beijing 100142, P.R. China.
Int J Mol Med. 2018 Apr;41(4):2128-2138. doi: 10.3892/ijmm.2018.3444. Epub 2018 Jan 30.
Human apurinic/apyrimidinic endonuclease 1 (APE1) is a ubiquitous multifunctional protein, which possesses DNA repair and redox activities. High levels of APE1 are associated with chemo‑ and radioresistance, and poor prognosis in various types of cancer, including non‑small cell lung cancer (NSCLC). Bu‑Fei decoction (BFD) is a traditional Chinese herbal formula, which is believed to supplement Qi, clear away heat and nourish the lungs. BFD and modified Bu‑Fei decoction (MBFD) have been used in China to treat patients with lung cancer. The present study aimed to evaluate the potential antitumor effects of BFD and MBFD on NSCLC in vitro and in vivo. In addition, the possible contribution of APE1 was examined. MTT assay was used to investigated the anti-tumor activity of BFD and MBFD on H1975 and H292 NSCLC cell lines. The DNA damage of cells in the control and the experimental groups was detected using comet assay. The in vivo anti-tumor effects of BFD and MBFD were evaluated in a NSCLC tumor nude mouse xenograft model. Polymerase chain reaction (PCR), reverse transcription‑quantitative PCR (RT‑qPCR) analysis and western blot analysis were applied to analyze the mRNA and protein expression levels of APE1 in H1975 and H292 cells, so as to the xenograft tumor tissues. The concentration of APE1 in mice plasma was determined using enzyme linked immunosorbent assay (ELISA). In vitro, BFD and MBFD inhibited the growth of cultured H1975 and H292 NSCLC cells. The results of a comet assay revealed that BFD and MBFD increased DNA damage. Furthermore, the expression levels of APE1 were decreased in response to BFD and MBFD at the mRNA and protein levels. In mice carrying NSCLC xenografts, BFD and MBFD inhibited tumor growth and decreased APE1 expression. In addition, in normal human lung bronchial epithelial BEAS‑2B cells, the half maximal inhibitory concentrations of BFD and MBFD were much higher compared with in NSCLC cells, and they had no effect on DNA damage. These results suggested that BFD and MBFD may inhibit the growth of NSCLC, possibly by inhibiting APE1 expression.
人源脱嘌呤/脱嘧啶核酸内切酶 1(APE1)是一种普遍存在的多功能蛋白,具有 DNA 修复和氧化还原活性。APE1 水平高与各种类型癌症的化疗和放疗耐药性以及预后不良相关,包括非小细胞肺癌(NSCLC)。补肺益肾汤(BFD)是一种中药方剂,被认为具有补气、清热和润肺的功效。BFD 和改良补肺益肾汤(MBFD)已在中国用于治疗肺癌患者。本研究旨在评估 BFD 和 MBFD 对 NSCLC 的体内外抗肿瘤作用,并探讨 APE1 的可能作用。MTT 法检测 BFD 和 MBFD 对 H1975 和 H292 NSCLC 细胞系的抗肿瘤活性。彗星试验检测细胞的 DNA 损伤。在 NSCLC 肿瘤裸鼠异种移植模型中评价 BFD 和 MBFD 的体内抗肿瘤作用。聚合酶链反应(PCR)、逆转录-定量 PCR(RT-qPCR)分析和蛋白质印迹分析用于分析 H1975 和 H292 细胞中 APE1 的 mRNA 和蛋白质表达水平,以及异种移植肿瘤组织。采用酶联免疫吸附试验(ELISA)测定小鼠血浆中 APE1 的浓度。体外,BFD 和 MBFD 抑制培养的 H1975 和 H292 NSCLC 细胞的生长。彗星试验结果表明,BFD 和 MBFD 增加了 DNA 损伤。此外,BFD 和 MBFD 下调了 APE1 在 mRNA 和蛋白质水平的表达。在携带 NSCLC 异种移植瘤的小鼠中,BFD 和 MBFD 抑制肿瘤生长并降低 APE1 表达。此外,在正常的人肺支气管上皮 BEAS-2B 细胞中,BFD 和 MBFD 的半数最大抑制浓度远高于 NSCLC 细胞,并且对 DNA 损伤没有影响。这些结果表明,BFD 和 MBFD 可能通过抑制 APE1 表达来抑制 NSCLC 的生长。