title: Growth inhibition and chemo-radiosensitization of head and neck squamous cell carcinoma (HNSCC) by survivin-siRNA lentivirus.
abstract: BACKGROUND
  Survivin expression is often associated with aggressive tumor behavior and therapy resistance. In this study, we investigated the effect of survivin knockdown by survivin-siRNA lentiviral vector (Svv-Lent) on the response of HNSCC to chemo-radiotherapy, tumor growth and metastasis.
  
  
  METHODS
  Four human HNSCC (OSC19, Cal27, Cal33 and FaDu) and one normal HOK cell lines were included in the study, and survivin knockdown was achieved with Svv-Lent treatment. Cell proliferation and apoptosis were measured by MTT and TUNEL assay, respectively. Transwell assays were performed to measure in vitro cell migration and matrigel invasion. Xenograft tumors were developed in nude mice by injecting Cal27 cells subcutaneously and following tail-vein injection of lung and liver metastasis.
  
  
  RESULTS
  Knockdown of survivin significantly suppressed HNSCC cell proliferation and induced apoptosis in vitro. Survivin inhibition could also significantly reduce in vitro cell migration and matrigel invasion that might be due to inactivation of matrix metalloproteinases. In vivo studies showed significant repression of Cal27 xenograft tumor growth and tissue metastasis leading to improvement in mice survival in the Svv-Lent treated group compared to controls. Our data indicated that survivin expression in HNSCC cells contributed to chemo-radioresistance, and its down-regulation increased anti-cancer effects of paclitaxel, cisplatin and radiation.
  
  
  CONCLUSIONS
  Our findings suggest that sustained survivin expression facilitates HNSCC tumor growth and confers resistance to chemo-radiotherapy. Svv-Lent therapy may be able to enhance the cytotoxic effect of commonly used anticancer drugs such as cisplatin and paclitaxel, and radiotherapy that could provide a promising strategy for the effective control of resistant head and neck cancer.
authors.affiliation: School of Studies in Biotechnology, Jiwaji University, Gwalior, India; Departments of Biomedical Sciences and Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, USA. Electronic address: zakirq.khan@gmail.com.
authors.forename: Zakir
authors.initials: Z
authors.lastname: Khan
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Abdul Arif
authors.initials: AA
authors.lastname: Khan
authors.affiliation: School of Studies in Biotechnology, Jiwaji University, Gwalior, India.
authors.forename: Godavarthi B K S
authors.initials: GB
authors.lastname: Prasad
authors.affiliation: Division of Plant-Microbe Interactions, National Botanical Research Institute, Lucknow, India.
authors.forename: Noor
authors.initials: N
authors.lastname: Khan
authors.affiliation: Diagnostic Division, Vanguard Diagnostics, New Delhi, India.
authors.forename: Ram Pramod
authors.initials: RP
authors.lastname: Tiwari
authors.affiliation: School of Studies in Biotechnology, Jiwaji University, Gwalior, India. Electronic address: psbisen@gmail.com.
authors.forename: Prakash Singh
authors.initials: PS
authors.lastname: Bisen
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000502:physiology; D059248:Chemoradiotherapy; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D055785:Gene Knockdown Techniques / Q000379:methods; D015316:Genetic Therapy / Q000379:methods*; D006258:Head and Neck Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D016086:Lentivirus / Q000235:genetics; D051379:Mice; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D017239:Paclitaxel / Q000008:administration & dosage; D034741:RNA, Small Interfering / Q000235:genetics*; D011836:Radiation Tolerance / Q000235:genetics; D000077022:Survivin; D023041:Xenograft Model Antitumor Assays / Q000379:methods
chemical_list: D000970:Antineoplastic Agents; C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering; D000077022:Survivin; D017239:Paclitaxel; D002945:Cisplatin
keywords: Apoptosis; Chemo-radioresistance; HNSCC; Lentiviral therapy; Survivin