PMID- 26545468 OWN - NLM STAT- MEDLINE DCOM- 20160819 LR - 20211203 IS - 1532-818X (Electronic) IS - 0196-0709 (Linking) VI - 36 IP - 6 DP - 2015 Nov-Dec TI - Improved therapeutic effectiveness by combining recombinant p14(ARF) with antisense complementary DNA of EGFR in laryngeal squamous cell carcinoma. PG - 763-71 LID - S0196-0709(15)00165-9 [pii] LID - 10.1016/j.amjoto.2015.07.012 [doi] AB - PURPOSE: The tumor suppressor p14(ARF) and proto-oncogene epidermal growth factor receptor (EGFR) play important roles in the development of laryngeal squamous cell carcinoma (LSCC). This study was aimed to determine whether combining recombinant p14(ARF) with antisense complementary DNA of EGFR could improve the therapeutic effectiveness in LSCC. MATERIALS AND METHODS: After human larynx cancer cells (Hep-2) were infected with recombinant adenoviruses (Ad-p14(ARF) and Ad-antisense EGFR) together or alone in vitro, the proliferation and cell cycle distribution of Hep-2 cells were detected by MTT assay and flow cytometer analysis, respectively. Furthermore, the antitumor effects of recombinant adenoviruses together or alone on Hep-2 xenografts were examined in vivo. The levels of p14(ARF) and EGFR expressed in Hep-2 cells and xenografts were determined by western blot assay. RESULTS: Ad-p14(ARF) combining with Ad-antisense EGFR markedly inhibited the Hep-2 proliferation compared with alone (P=0.001, P=0.002 respectively). Combination of Ad-p14(ARF) and Ad-antisense EGFR led to the proportion of Hep-2 cells in G0/G1 phases increased by up to 86.9%. The down-expression of EGFR protein and overexpression of p14(ARF) protein were observed in vitro and in vivo, and this effect was preserved when Ad-p14(ARF) was combined with Ad-antisense EGFR. Besides, Ad-p14(ARF) plus Ad-antisense EGFR significantly (P<0.05) increased the antitumor activity against Hep-2 tumor xenografts comparing with Ad-p14(ARF) or Ad-antisense EGFR alone. CONCLUSION: Combination Ad-p14(ARF) with Ad-antisense EGFR significantly increased the antitumor responses in LSCC. An effectively potential gene therapy to prevent proliferation of LSCC was provided. CI - Copyright (c) 2015 Elsevier Inc. All rights reserved. FAU - Liu, Feng AU - Liu F AD - West China School of Medicine, West China Hospital, Sichuan University Department of Otorhinolaryngology, Chengdu, People's Republic of China. FAU - Du, JinTao AU - Du J AD - West China School of Medicine, West China Hospital, Sichuan University Department of Otorhinolaryngology, Chengdu, People's Republic of China. FAU - Xian, Junming AU - Xian J AD - West China School of Medicine, West China Hospital, Sichuan University Department of Otorhinolaryngology, State Key Laboratory of Biotherapy, Chengdu, People's Republic of China. Electronic address: fxjming@163.com. FAU - Liu, Yafeng AU - Liu Y AD - West China School of Medicine, West China Hospital, Sichuan University Department of Otorhinolaryngology, Chengdu, People's Republic of China. FAU - Liu, Shixi AU - Liu S AD - West China School of Medicine, West China Hospital, Sichuan University Department of Otorhinolaryngology, Chengdu, People's Republic of China. FAU - Lin, Yan AU - Lin Y AD - Department of Otorhinolaryngology, the First Affiliated Hospital of Kunming Medical College, Kunming, China. LA - eng PT - Journal Article DEP - 20150805 PL - United States TA - Am J Otolaryngol JT - American journal of otolaryngology JID - 8000029 RN - 0 (DNA, Antisense) RN - 0 (MAS1 protein, human) RN - 0 (Proto-Oncogene Mas) RN - 0 (Tumor Suppressor Protein p14ARF) RN - EC 2.7.10.1 (ErbB Receptors) SB - IM MH - Adenoviridae/genetics MH - Carcinoma, Squamous Cell/*pathology/therapy MH - Cell Cycle MH - Cell Line, Tumor MH - Cell Proliferation MH - DNA, Antisense/*genetics MH - ErbB Receptors/*genetics MH - Genetic Therapy MH - Genetic Vectors MH - Humans MH - Laryngeal Neoplasms/*pathology/therapy MH - Proto-Oncogene Mas MH - Transfection MH - Tumor Suppressor Protein p14ARF/*genetics EDAT- 2015/11/08 06:00 MHDA- 2016/08/20 06:00 CRDT- 2015/11/08 06:00 PHST- 2015/05/29 00:00 [received] PHST- 2015/07/15 00:00 [revised] PHST- 2015/07/31 00:00 [accepted] PHST- 2015/11/08 06:00 [entrez] PHST- 2015/11/08 06:00 [pubmed] PHST- 2016/08/20 06:00 [medline] AID - S0196-0709(15)00165-9 [pii] AID - 10.1016/j.amjoto.2015.07.012 [doi] PST - ppublish SO - Am J Otolaryngol. 2015 Nov-Dec;36(6):763-71. doi: 10.1016/j.amjoto.2015.07.012. Epub 2015 Aug 5.