الفهرس 
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Abstract
Summary
Oral squamous cell carcinoma (OSCC) is the main malignant neoplasm of the oral cavity accounting for almost 90% of all oral malignancies and the sixth most common cancer worldwide, with variations in its global incidence (Jemal et al., 2011).
The main causes of OSCC include excessive alcohol intake and tobacco use. Exposure to sunlight is a causative factor for cancer of the lips, which is similar to that for skin cancer. Human papilloma virus is also a risk factor for causing oral cancer. Immu¬nosuppressed patients like human immunodeficiency virus and renal transplant patients have the highest risk factor for developing oral cancer (Chitapanarux et al., 2006, Ragin et al., 2007 and Jones and Rankin, 2008).
Among the modalities currently available for OSCC treatment, chemotherapy has been a primary option for managing advanced-stage including metastatic and recurrent cancer. The major advantage of the clinical use of chemotherapy over surgery and radiation is its systemic action which kills cancer cells in both primary and metastatic tumors (Scully et al., 2013).
Doxorubicin is a well-known chemotherapeutic agent which is used in treatment of a wide variety of cancers. It prevents the replication and transcription of DNA through intercalating between base pairs of the DNA strands, inhibition of the topoisomerase II enzyme and formation of iron-mediated oxygen free radicals that cause oxidative damage to DNA, proteins, and cell membrane lipids (Caroline et al., 2011 and Oktay et al., 2013).
Although the higher cytotoxic efficacy of doxorubicin its uses have been diminished due to the side effects. One of the successful efforts has involved the encapsulation of doxorubicin within liposomes to overcome these side effects and increase the effectiveness (Ramsay, 2005 and Bae et al., 2011).
Pegylated liposomal doxorubicin (Doxil®) a unique formulation of doxorubicin consists of unilamellar liposomes with a coating of methoxy-polyethylene glycol (mPEG). Liposomal coating of doxorubicin favors drug stability, minimizes drug loss during blood circulation, enhances accumulation in tumors and decreases side effects (Sidone, 2011).
The current study was constructed to investigate the in vitro effect of doxorubicin and its nano formulation pegylated liposomal doxorubicin (Doxil®) on the human tongue squamous carcinoma cell line (Scc-27).
They cytotoxic effect was evaluated with MTT assay, while the mode of cell death was assessed with acridine orange/ethidium bromide fluorescence stain also caspase-3 evaluated with indirect ELISA and c- Myc oncogene expression was assessed by PCR.
MTT assay showed that both doxorubicin and doxil are cytotoxic to SCC27 but doxorubicin is more effective and the doses of doxorubicin were (1.7- 5.2) folds lower than doxil.
Staining of treated SCC27 cells with acridine orange/ethidium bromide fluorescence stain showed that most of cells treated with doxil expressed apoptotic stain while in case of doxorubicin the percentage of necrotic and apoptotic cells were nearly equal.
Evaluation of caspase-3 apoptotic marker with ELISA technique was used to confirm the findings of fluorescence stain. Caspase-3 level was increased when SCC27 cells were individually treated with doxorubicin and doxil. The caspase-3 level was (1.4 folds) higher in doxil than doxorubicin.
from the MTT assay, fluorescence staining and caspase-3 evaluation we can conclude that nano-formulation of doxorubicin may enhance its proapoptotic efficacy rather than increase cytotoxicity.
To evaluate the possible effect of doxorubicin on the oncogenic signaling pathways, c-Myc oncogene was evaluated using PCR.
Treatment of SCC27 cells with doxorubicin and doxil showed a significant inhibition in c-Myc expression. The percentage of c-Myc mRNA expression was higher (1.3 fold) in doxorubicin treated cells compared to doxil.
from PCR findings we can suggest that nano- formulation of doxorubicin may enhance the interference with c-Myc oncogenic pathway.