Liu Xing, Yang Zhiguang, Li Yiquan, Zhu Yilong, Li Wenjie, Li Shanzhi, Wang Jing, Cui Yingli, Shang Chao, Liu Zirui, Song Gaojie, Li Ce, Li Xiao, Shao Guoguang, Jin Ningyi
Department of Thoracic Surgery, The First Hospital of Jilin University, Changchun, China.
Institute of Military Veterinary Medicine, Academy of Military Medical Science, Changchun, China.
Front Oncol. 2020 Feb 25;10:229. doi: 10.3389/fonc.2020.00229. eCollection 2020.
Oncolytic virotherapy is emerging as an important agent in cancer treatment. In a previous study, we designed and constructed Ad-Apoptin-hTERTp-E1a (Ad-VT), a dual cancer-selective anti-tumor recombinant adenovirus. In this study, crystal violet staining and WST-1 assays showed that Ad-VT has a significant tumor killing effect in a time and dose dependent manner. The combination of Ad-VT (10 MOI) and gemcitabine (10 nM) significantly inhibited NCI-H226 cells, but did not increase the killing effect of gemcitabine on human normal bronchial epithelial cells BEAS-2B. Hoechst, JC-1 and Annexin V experiments demonstrated that the combination of Ad-VT and gemcitabine mainly inhibited NCI-H226 cell proliferation by inducing apoptosis (mitochondrial pathway). The combination also significantly inhibited the migration and invasion abilities of NCI-H226 cells. , Ad-VT in combination with low-dose gemcitabine could effectively inhibit tumor growth and prolong survival of mice. Ad-VT has the characteristics of tumor-selective replication and killing, and . The combined application of Ad-VT and gemcitabine has a synergistic effect, which can increase the anti-tumor effect and reduce the toxicity of chemotherapy drugs, indicating that Ad-VT has a potential clinical value in the treatment of lung squamous cell carcinoma.
溶瘤病毒疗法正在成为癌症治疗中的一种重要手段。在先前的一项研究中,我们设计并构建了Ad-Apoptin-hTERTp-E1a(Ad-VT),一种双重癌症选择性抗肿瘤重组腺病毒。在本研究中,结晶紫染色和WST-1检测表明Ad-VT具有显著的肿瘤杀伤作用,呈时间和剂量依赖性。Ad-VT(10 MOI)与吉西他滨(10 nM)联合使用可显著抑制NCI-H226细胞,但并未增强吉西他滨对人正常支气管上皮细胞BEAS-2B的杀伤作用。Hoechst、JC-1和Annexin V实验表明,Ad-VT与吉西他滨联合使用主要通过诱导凋亡(线粒体途径)抑制NCI-H226细胞增殖。该联合用药还显著抑制了NCI-H226细胞的迁移和侵袭能力。此外,Ad-VT与低剂量吉西他滨联合使用可有效抑制肿瘤生长并延长小鼠生存期。Ad-VT具有肿瘤选择性复制和杀伤的特性,并且Ad-VT与吉西他滨联合应用具有协同作用,可增强抗肿瘤效果并降低化疗药物的毒性,表明Ad-VT在肺鳞状细胞癌治疗中具有潜在的临床价值。