College of Life Sciences and Bio-Engineering, Beijing University of Technology, Beijing, 100022, China.
Beijing Institute of Technology, Beijing, 100124, China.
J Cancer Res Clin Oncol. 2020 Apr;146(4):861-874. doi: 10.1007/s00432-020-03157-2. Epub 2020 Feb 22.
Non-small cell lung cancer (NSCLC) is the most common type of lung cancer and ranked top in terms of incidence and mortality in men and women. Recently, improvements in treatment approaches for NSCLC have reported, but still, there is a need to devise innovative treatment strategies, especially to manage the advanced and metastatic stage of NSCLC. Aloperine (ALO), an herbal alkaloid, has exerted anti-cancer effects in many cancers. However, the use of any chemotherapeutic agents is dose limited due to possible adverse effects and drug-resistance issues. Therefore, a combination of chemotherapy with viral-based targeted gene therapy may provide a novel treatment strategy for NSCLC.
METHODS/RESULTS: In this study, the results of the MTT and flow cytometry-based assays showed that Aloperine-Adbic (adenoviral vector expressing p14/p53) combined treatment on NSCLC cells synergistically produced anti-proliferative effects, induced apoptosis, and arrested cell cycle at the G1 phase. Furthermore, the expression analysis suggested that the p53/p21 pathway might contribute to achieving aforesaid cytotoxic effects. The ALO-Adbic combined treatment prolonged the percent survival of NSCLC xenograft models.
In conclusion, ALO-Adbic combination can produce synergistic anti-cancer effects at low doses, and may offer a more effective and less toxic new treatment strategy for NSCLC.
非小细胞肺癌(NSCLC)是最常见的肺癌类型,无论男性还是女性,其发病率和死亡率均位居首位。近年来,NSCLC 的治疗方法有所改进,但仍需要设计创新的治疗策略,尤其是在管理晚期和转移性 NSCLC 方面。小檗碱(ALO)是一种植物生物碱,在许多癌症中具有抗癌作用。然而,由于可能出现不良反应和耐药性问题,任何化疗药物的使用都受到剂量限制。因此,化疗联合基于病毒的靶向基因治疗可能为 NSCLC 提供一种新的治疗策略。
方法/结果:在这项研究中,MTT 和流式细胞术检测结果表明,小檗碱-Adbic(表达 p14/p53 的腺病毒载体)联合处理 NSCLC 细胞可协同产生抗增殖作用,诱导细胞凋亡,并将细胞周期阻滞在 G1 期。此外,表达分析表明,p53/p21 通路可能有助于实现上述细胞毒性作用。ALO-Adbic 联合治疗延长了 NSCLC 异种移植模型的存活百分比。
总之,ALO-Adbic 联合治疗可以在低剂量下产生协同的抗癌作用,为 NSCLC 提供一种更有效、毒性更小的新治疗策略。