title: An oncolytic adenovirus expressing interleukin-24 enhances antitumor activities in combination with paclitaxel in breast cancer cells.
abstract: Oncolytic adenoviruses are a novel class of anticancer treatment, based upon their ability to replicate selectively within malignant cells resulting in cell lysis. The replication‑selective adenovirus, ZD55‑IL‑24, was constructed by harboring an E1B‑55 kDa deletion and arming with interleukin-24 (IL-24). The microtubule‑stabilizing drug paclitaxel (PTX) exhibits activity in relapsed cancer. In the present study, the synergistic antitumor effects of the combination of PTX and ZD55‑IL‑24 on breast cancer cells was investigated. The results demonstrated that there were different roles for PTX in the expression of transgenic mRNA and protein. ZD55‑IL‑24 combined with PTX induced marked growth inhibition of MDA‑MB‑231 and Bcap‑37 cells. PTX increased viral uptake and appeared not to alter the replication of ZD55‑IL‑24 in breast cancer cells. Annexin V‑fluorescein isothiocyanate/propidium iodide staining and the Hoechst 33258 assay indicated that ZD55‑IL‑24 induced an increase in the number of apoptotic cells when administered in combination with PTX. It was demonstrated that ZD55‑IL‑24 conjugated with PTX was highly concomitant, and increased proapoptotic proteins levels, activated caspase‑3, -7 and -9 and downregulated anti‑apoptotic proteins. These results suggested that ZD55‑IL‑24 in combination with PTX exhibited a markedly increased cytotoxic and apoptosis‑inducing effect in breast cancer cells. Thus, this chemo‑gene‑viro therapeutic strategy was demonstrated to be superior to conventional chemotherapy or gene‑viro therapy alone.
authors.affiliation: Jiangsu Key Laboratory of Biological Cancer Therapy, Xuzhou Medical College, Xuzhou, Jiangsu 221002, P.R. China.
authors.forename: Lin
authors.initials: L
authors.lastname: Fang
authors.forename: Qian
authors.initials: Q
authors.lastname: Cheng
authors.forename: Jin
authors.initials: J
authors.lastname: Bai
authors.forename: Ying-Dong
authors.initials: YD
authors.lastname: Qi
authors.forename: Jun-Jie
authors.initials: JJ
authors.lastname: Liu
authors.forename: Lian-Tao
authors.initials: LT
authors.lastname: Li
authors.forename: Jun-Nian
authors.initials: JN
authors.lastname: Zheng
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D017209:Apoptosis; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D049109:Cell Proliferation; D003131:Combined Modality Therapy; D004357:Drug Synergism; D005260:Female; D006801:Humans; D007378:Interleukins / Q000235:genetics*; D050130:Oncolytic Virotherapy; D017239:Paclitaxel / Q000627:therapeutic use*; D000091402:Prohibitins; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D014779:Virus Replication / Q000187:drug effects; D000099180:Interleukin-24
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D007378:Interleukins; D017239:Paclitaxel; D000091402:Prohibitins; D012333:RNA, Messenger; D000099180:Interleukin-24; C000717331:PHB2 protein, human