Zakir Khan1, Abdul Arif Khan2, Godavarthi B K S Prasad3, Noor Khan4, Ram Pramod Tiwari5, Prakash Singh Bisen6. 1. 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. 2. Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. 3. School of Studies in Biotechnology, Jiwaji University, Gwalior, India. 4. Division of Plant-Microbe Interactions, National Botanical Research Institute, Lucknow, India. 5. Diagnostic Division, Vanguard Diagnostics, New Delhi, India. 6. School of Studies in Biotechnology, Jiwaji University, Gwalior, India. Electronic address: psbisen@gmail.com.
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.
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: Sagar Shelake; Umesh T Sankpal; W Paul Bowman; Matthew Wise; Anish Ray; Riyaz Basha Journal: Invest New Drugs Date: 2016-12-26 Impact factor: 3.850
Authors: Zakir Khan; Abdul Arif Khan; Hariom Yadav; Godavarthi B K S Prasad; Prakash Singh Bisen Journal: Cell Mol Biol Lett Date: 2017-04-05 Impact factor: 5.787