The cancer-targeting gene virotherapy might be a useful strategy for the treatment of cancer, because it could combine the advantages of both gene therapy and virotherapy. This study aimed to construct a triple-regulated oncolytic adenovirus, Ad-RGD-Survivin-ZD55-miR-143, carrying the therapeutic gene miR-143 and evaluate its possible antitumor effect in colorectal cancer. We observed that miR-143 was lowly expressed in patients with colorectal cancer. The upregulation of miR-143 could inhibit cell proliferation and induce cell apoptosis by targeting KRAS in colorectal cancer cells. Then, Ad-RGD-Survivin-ZD55-miR-143 was successfully constructed in this study. Cells infected with Ad-RGD-Survivin-ZD55-miR-143 could inhibit cell proliferation, suppress cell migration and invasion, arrest cells at the G1 phase, and induce cellular apoptosis. At the same time, Ad-RGD-Survivin-ZD55-miR-143 decreased the expression of PARP-1 and KRAS protein in vitro. In a HCT116 xenograft model, intratumoral injection of Ad-RGD-Survivin-ZD55-miR-143 resulted in reduced tumor growth. Furthermore, Ad-RGD-Survivin-ZD55-miR-143 induced apoptosis and decreased the expression level of KRAS in HCT116 xenograft cells. Our results suggested that Ad-RGD-Survivin-ZD55-miR-143 produced a strong antitumor effect by targeting KRAS and that this strategy could broaden the therapeutic options for treating colorectal cancer.

靶向癌症的基因病毒疗法可能是治疗癌症的有用策略，因为它可以结合基因疗法和病毒疗法的优势。这项研究旨在构建携带治疗基因miR-143的三重调控溶瘤腺病毒Ad-RGD-Survivin-ZD55-miR-143，并评估其在结肠直肠癌中可能的抗肿瘤作用。我们观察到miR-143在结直肠癌患者中的表达较低。miR-143的上调可通过靶向KRAS在结直肠癌细胞中抑制细胞增殖并诱导细胞凋亡。然后，在该研究中成功构建了Ad-RGD-Survivin-ZD55-miR-143。用Ad-RGD-Survivin-ZD55-miR-143感染的细胞可以抑制细胞增殖，抑制细胞迁移和侵袭，将细胞阻滞在G1期，并诱导细胞凋亡。体外。在HCT116异种移植模型中，肿瘤内注射Ad-RGD-Survivin-ZD55-miR-143导致肿瘤生长减少。此外，Ad-RGD-Survivin-ZD55-miR-143诱导了HCT116异种移植细胞的凋亡并降低了KRAS的表达水平。我们的结果表明，Ad-RGD-Survivin-ZD55-miR-143通过靶向KRAS产生了强大的抗肿瘤作用，并且该策略可以拓宽治疗结直肠癌的治疗选择。