In vivo and in vitro inhibition of SCLC by combining dual cancer-specific recombinant adenovirus with Etoposide

文献类型： 外文期刊

第一作者： Li, Tingyu

作者： Li, Tingyu;Fang, Jinbo;Li, Yiquan;Zhu, Yilong;Li, Shanzhi;Xiu, Zhiru;Li, Yaru;Jin, Ningyi;Zhu, Guangzhe;Li, Xiao;Li, Tingyu;Fang, Jinbo;Li, Yiquan;Zhu, Yilong;Li, Shanzhi;Jin, Ningyi;Li, Xiao;Chu, Jihao;Liu, Xing;Jin, Ningyi;Li, Xiao;Sun, Lili

作者机构：

关键词： Recombinant adenovirus; Etoposide; Small cell lung cancer; Synergy

期刊名称：JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY （ 影响因子：4.322； 五年影响因子：4.176 ）

ISSN： 0171-5216

年卷期： 2022 年 148 卷 5 期

页码：

收录情况： SCI

摘要： Purpose 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. Methods 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. Results 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. Conclusions The above results indicate that when combined with Etoposide, Ad-VT may have an important role in synergistically inhibiting tumors.

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