Academician Workstation of Jilin Province, Changchun University of Chinese Medicine, Jingyue Economic and Technological Development Zone, No. 1035, Boshuo Road, Changchun, 130117, Jilin, People's Republic of China.
Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, 130122, People's Republic of China.
J Cancer Res Clin Oncol. 2022 May;148(5):1073-1085. doi: 10.1007/s00432-021-03899-7. Epub 2022 Jan 17.
Oncolytic virotherapy is emerging as an important modality 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.
To explore the therapeutic effect of recombinant adenovirus Ad-VT together with Etoposide on small cell lung cancer, the ability of Ad-VT alone, Etoposide alone, and a combination of Ad-VT + Etoposide to inhibit proliferation of NCI-H446 and BEAS-2B cells was investigated using the WST-1 method. According to the inhibitory action of different combinations, a combination index (CI) was estimated by CalcuSyn software to select the best combination. The inhibitory effect of Ad-VT combined with Etoposide on NCI-H446 and BEAS-2B cells was detected by crystal violet staining and the CFST method. Hoechst, Annexin V and JC-1 staining were used to explore the inhibitory pathway of Ad-VT combined with Etoposide on NCI-H446 cells. The migratory and invasive abilities of treated NCI-H446 cells were assessed by Transwell and BioCat methods. Tumor volume, body weight and survival rate were measured to analyze the anti-tumor and toxic effects of different treatments in tumor-bearing mice.
Ad-VT (20 MOI) combined with Etoposide (400 nM) significantly inhibited NCI-H446 cell proliferation with reduced toxicity of Etoposide to normal cells. Ad-VT induced apoptosis of NCI-H446 cells mainly through the mitochondrial apoptosis pathway, an effect significantly increased by the combined treatment. Ad-VT together with Etoposide significantly inhibited migration and invasion of NCI-H446 cells, inhibited tumor growth in vivo and prolonged the survival of tumor-bearing mice.
The above results indicate that when combined with Etoposide, Ad-VT may have an important role in synergistically inhibiting tumors.
溶瘤病毒治疗法作为癌症治疗的一种重要手段正在兴起。在之前的研究中，我们设计并构建了一种双肿瘤选择性抗瘤重组腺病毒 Ad-Apoptin-hTERTp-E1a（Ad-VT）。
为了探讨重组腺病毒 Ad-VT 联合依托泊苷（Etoposide）对小细胞肺癌的治疗作用，采用 WST-1 法研究 Ad-VT 单独、Etoposide 单独以及 Ad-VT+Etoposide 联合对 NCI-H446 和 BEAS-2B 细胞增殖的抑制作用。根据不同组合的抑制作用，用 CalcuSyn 软件估算联合指数（CI），以选择最佳组合。采用结晶紫染色和 CFST 法检测 Ad-VT 联合 Etoposide 对 NCI-H446 和 BEAS-2B 细胞的抑制作用。采用 Hoechst、Annexin V 和 JC-1 染色法探讨 Ad-VT 联合 Etoposide 对 NCI-H446 细胞的抑制途径。采用 Transwell 和 BioCat 法检测处理后的 NCI-H446 细胞的迁移和侵袭能力。通过测量肿瘤体积、体重和存活率来分析荷瘤小鼠不同治疗方法的抗肿瘤和毒性作用。
Ad-VT（20 MOI）联合 Etoposide（400 nM）显著抑制 NCI-H446 细胞增殖，同时降低 Etoposide 对正常细胞的毒性。Ad-VT 主要通过线粒体凋亡途径诱导 NCI-H446 细胞凋亡，联合治疗可显著增强该作用。Ad-VT 联合 Etoposide 显著抑制 NCI-H446 细胞的迁移和侵袭，抑制体内肿瘤生长，延长荷瘤小鼠的生存时间。
上述结果表明，Ad-VT 与 Etoposide 联合应用时可能在协同抑制肿瘤方面发挥重要作用。
