Combination of oncolytic adenovirus and luteolin exerts synergistic antitumor effects in colorectal cancer cells and a mouse model

Abstract

In recent years, oncolytic viruses have attracted increasing interest due to their potent antitumor effects. Luteolin, a natural product, has additionally been observed to exhibit various pharmacological antitumor activities. Previously, a novel dual-targeting oncolytic adenovirus, complement decay-accelerating factor (CD55)-tumor necrosis factor ligand superfamily member 10 (TRAIL), was constructed, which exhibited significant growth inhibitory effects in various types of tumor cell. The present study investigated whether the combination of luteolin and CD55-TRAIL was able to exert a synergistic antitumor effect in colorectal carcinoma (CRC) cells. The cytotoxicity and tumor cell apoptosis mediated by combination treatment in CRC cells were detected via an MTT assay, Hoechst staining and western blotting, respectively. Tumor growth in vivo was examined in a CRC mouse xenograft model following various treatments. The results demonstrated that the addition of luteolin enhanced oncolytic adenovirus-mediated enhanced green fluorescent protein, early region 1A and TRAIL expression. The combination of CD55-TRAIL with luteolin synergistically inhibited tumor growth and promoted CRC cellular apoptosis in vitro and in vivo. Additionally, the combination of CD55-TRAIL with luteolin significantly decreased cytotoxicity in lung/bronchial normal epithelial cells, compared with single treatment. Therefore, the combination of CD55-TRAIL with luteolin may be a novel efficient therapeutic strategy for CRC in the future.

Luteolin enhances the antitumor efficacy of oncolytic vaccinia virus that harbors IL‐24 gene in liver cancer cells

“…18 Besides, luteolin enhances the expression of oncolytic adenovirus-mediated E1A and TRAIL proteins, which leads to augment antitumor effects by enhancing colorectal cancer cells apoptosis. 19 In this present study, the combination of VV-IL-24 and luteolin markedly decreased viability and significantly increased liver cancer cells apoptosis. The mechanism was explored to provide a novel strategy on the apply of VV-IL-24 and luteolin in the therapy of liver cancer.…”

Oncolytic Adenovirus CD55-Smad4 Suppresses Cell Proliferation, Metastasis, and Tumor Stemness in Colorectal Cancer by Regulating Wnt/β-Catenin Signaling Pathway

“…For example, the combination of the oncolytic adenovirus ICOVIR-5 with chemotherapy produces an enhanced anti-glioma effect in vivo [ 59 ]. Oncolytic adenovirus and luteolin administered together exert synergistic anti-tumor effects against colorectal cancer cells and in a mouse model of CRC [ 22 ]. Oncolytic adenovirus carrying XAF1 and cisplatin synergistically suppress the growth of hepatocellular carcinoma [ 60 ].…”

“…Cell apoptosis was determined using Annexin V FITC/PI (BD Biosciences, San Jose, CA, USA) using our previously described protocol [ 22 ]. In short, 5 × 10 5 cells were inoculated into each well of 6-well plates, cultured for 12 h, and then treated with CD55-EGFP and CD55-Smad4 for an additional 48 h. Subsequently, the cells were harvested by trypsinization, resuspended in 500 µL of binding buffer, and stained with FITC-labeled annexin V and propidium iodide.…”

“…Animal experiments complied with the regulations and standards set by the US Department of Agriculture and the National Institutes of Health and were performed according to previously described protocols [ 22 ]. The study was approved by the Laboratory Animal Welfare Ethics Committee of the Zhejiang Sci-Tech University (No.…”

Doxorubicin hydrochloride enhanced antitumour effect of CEA‐regulated oncolytic virotherapy in live cancer cells and a mouse model

“…These disadvantages of oncolytic adenoviruses need to be further resolved. Thus, the various combination therapies with oncolytic adenovirus were proposed, such as nanomaterial‐oncolytic adenovirus combination therapy, 25,26 immunocyto‐oncolytic virus combination therapy 27‐29 and chemotherapeutic drug‐oncolytic virus 30‐33 . These combination strategies provide new ideas for future oncolytic virotherapy of tumours.…”