Wang Mingjuan, Hong Yanling, Feng Qiang, Pan Xinyan, Song Shuling, Cui Jing, Lei Jin, Fang Hong, Yang Julun
Kunming Medical University, Kunming, Yunnan Province, China.
Department of Pathology, Kunming General Hospital, Kunming 650032, Yunnan Province, China.
Mol Ther Oncolytics. 2018 Oct 23;11:90-101. doi: 10.1016/j.omto.2018.10.003. eCollection 2018 Dec 21.
The development of gastric cancer is frequently related to the overexpression of wild-type p21 proteins, but it is rarely related to mutated Ras proteins. We previously constructed a broad-spectrum anti-p21-Ras single-chain variable fragment antibody (scFv), which was carried by the oncolytic adenovirus KGHV500. Here we explored the antitumor effects of this recombinant oncolytic adenovirus carried by cytokine-induced killer (CIK) cells on human gastric SGC7901 cells that overexpress wild-type Ras. The MTT assay, scratch test, Transwell assay, and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay were performed to investigate the proliferation, migration, invasiveness, and cell apoptosis rate, respectively, of the human gastric cell line SGC7901 treated with KGHV500 adenovirus. Then, the tumor-targeting ability and systemic safety of KGHV500 adenovirus delivered by CIK cells were explored . We found that KGHV500 adenovirus could significantly inhibit proliferation, migration, and invasiveness and promote cell apoptosis in SGC7901 cells . studies showed that CIK cells could successfully deliver KGHV500 adenovirus to the tumor site; the two vectors synergistically killed tumor cells, and the treatment was relatively safe for normal tissues. In conclusion, this therapeutic strategy of recombinant adenovirus KGHV500 delivered by CIK cells offers a positive prospect for the targeted therapy of Ras-related cancers.
胃癌的发生发展常常与野生型p21蛋白的过表达有关，但很少与突变的Ras蛋白有关。我们之前构建了一种广谱抗p21-Ras单链可变片段抗体（scFv），其由溶瘤腺病毒KGHV500携带。在此，我们探讨了由细胞因子诱导的杀伤细胞（CIK）携带的这种重组溶瘤腺病毒对过表达野生型Ras的人胃癌SGC7901细胞的抗肿瘤作用。进行MTT法、划痕试验、Transwell试验和末端脱氧核苷酸转移酶介导的dUTP缺口末端标记（TUNEL）试验，分别研究用KGHV500腺病毒处理的人胃癌细胞系SGC7901的增殖、迁移、侵袭和细胞凋亡率。然后，探讨CIK细胞递送的KGHV500腺病毒的肿瘤靶向能力和全身安全性。我们发现KGHV500腺病毒可显著抑制SGC7901细胞的增殖、迁移和侵袭，并促进细胞凋亡。研究表明，CIK细胞可成功将KGHV500腺病毒递送至肿瘤部位；两种载体协同杀伤肿瘤细胞，且该治疗对正常组织相对安全。总之，CIK细胞递送重组腺病毒KGHV500的这种治疗策略为Ras相关癌症的靶向治疗提供了积极的前景。
