title: Increase of the therapeutic effect by treating nasopharyngeal tumor with combination of HER-2 siRNA and paclitaxel.
abstract: Therapeutic agents targeting HER-2/neu have been intensively addressed over the past decades. Previously, we reported that HER-2 synthetic small interfering RNA (HER-2 siRNA) could suppress the growth of human nasopharyngeal KB tumor xenografts by intratumoral injection with lipid-based nanoparticles; however, complete regression of the tumor was not achieved. In this study, we investigated antitumor activity by RNA interference in combination with paclitaxel (PTX) for KB cells using HER-2 siRNA and HER-2 short hairpin RNA-expressing plasmid DNA (HER-2 shRNA pDNA). Suppression of HER-2 expression by siRNA or shRNA pDNA caused significant reduction of proliferation by inducing apoptosis and enhancing the sensitivity for PTX in HER-2 positive KB cells. Interestingly, an HER-2 antibody trastuzumab could not increase the antitumor effect by PTX in KB xenografts. Combination therapy by intratumoral injection of HER-2 siRNA or HER-2 shRNA pDNA with PTX significantly inhibited the tumor growth of xenografts compared with each therapy used individually. In particular, HER-2 shRNA pDNA plus PTX largely extended the mean survival days compared with HER-2 siRNA plus PTX. Collectively, these findings suggest that HER-2 shRNA-based combined therapy with PTX could be a novel strategy to inhibit the progression of HER-2-positive cancer.
authors.affiliation: Institute of Medicinal Chemistry, Hoshi University, Shinagawa-ku, Tokyo 142-8501, Japan. yhattori@hoshi.ac.jp
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Hattori
authors.forename: Motoki
authors.initials: M
authors.lastname: Hakoshima
authors.forename: Kimiko
authors.initials: K
authors.lastname: Koga
authors.forename: Yoshie
authors.initials: Y
authors.lastname: Maitani
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D017024:Chemotherapy, Adjuvant; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D051379:Mice; D009303:Nasopharyngeal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D017239:Paclitaxel / Q000494:pharmacology*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D013997:Time Factors; D014162:Transfection; D000068878:Trastuzumab; D047368:Tumor Burden; D023041:Xenograft Model Antitumor Assays
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D017239:Paclitaxel; D034741:RNA, Small Interfering; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human