Comparison of injectable doxorubicin & its nanodrug complex chemotherapy for the treatment of 4-nitroquinoline-1-oxide induced oral squamous cell carcinoma in rats.

BACKGROUND & OBJECTIVES: Combination treatments of chemotherapy and nanoparticle drug delivery have shown significant promise in cancer treatment. The aim of the present study was to compare the efficacy of a nanodrug complex with its free form in the treatment of tongue squamous cell carcinoma induced by 4-nitroquinoline-1-oxide in rats. METHODS: In this study, 75 male Sprague-Dawley rats were divided into five groups. Oral squamous cell carcinoma (OSCC) was induced by using 4- nitroquinoline-1-oxide (4NQO) as a carcinogen. Newly formulated doxorubicin (DOX)-methotrexate (MTX)-loaded nanoparticles, and free DOX-MTX were administrated intravenously to rats. During the study, the animals were weighed once a week. At the end of the treatment, rats' tongues were evaluated histopathologically. RESULTS: There was significant difference between the mean weight of rats in groups A and B (P=0.001) and also groups A and K (P<0.001). No significant association was found between the mortality rate of groups. The difference between the severity of dysplasia of treated and untreated groups was significant (P<0.001). INTERPRETATION & CONCLUSIONS: Our study showed that DOX-MTX nanoparticle complex was more effective than free DOX-MTX in chemotherapy treatment of oral squamous cell carcinoma in rat models. Further investigations are necessary to clarify the advantages and disadvantages of the nanoparticle complex and its potential therapeutic application for different types of cancer.

Therapeutic Efficacy of Orally Delivered Doxorubicin Nanoparticles in Rat Tongue Cancer Induced by 4-Nitroquinoline 1-Oxide.

PURPOSE: Oral cancer is one of the most significant cancers in the world, and squamous cell carcinoma makes up about 94% of oral malignancies. The aim of the present study was to compare the efficacy of doxorubicin plus methotrexate - loaded nanoparticles on tongue squamous cell carcinoma induced by 4NQO and compare it with the commercial doxorubicin and methotrexate delivered orally on seventy SD male rats. METHODS: 70 rats were divided into five groups. During the study, the animals were weighed by a digital scale once a week. Number of mortalities was recorded in the data collection forms. At the end of the treatment, biopsy samples were taken from rat tongues in order to evaluate the severity of dysplasia and the extent of cell proliferation. The results were analyzed using ANOVA, descriptive statistics and chi-square test. RESULTS: No statistically significant difference was found in the mean weight of five groups (p>0.05). No significant relationship was found between groups and mortality rate (P = 0. 39). In addition, there was a significant relationship between groups and the degree of dysplasia (P <0.001). The statistical analysis showed a significant relationship between groups and the rate of cell proliferation (p <0.001). CONCLUSION: The results of the present study showed that the use of doxorubicin plus methotrexate - loaded nanoparticles orally had more therapeutic effects than commercial doxorubicin plus methotrexate.

Evaluation of the Effect of Two Systemic Doses of HESA-A on Prevention of Induced Tongue Neoplasm in Rats.

Background and aims. The aim of the present study was to compare the inhibitory effects of two systemic doses of HESA-A on prevention of 4-NQO-induced tongue neoplasms in rats. This study evaluated weight and histopathological changes. Materials and methods. Forty-eight male Sprague Dawley rats were divided into four groups of A, B, C and D of each 12 rats. The rats in groups B to D received 30 ppm of 4-Nitroquinoline-1-oxide (4-NQO) in drinking water for 12 weeks.  When feeding with 4-NQO was initiated, the rats in groups B and C received HESA-A at doses of 250 and 500 mg/kg, respectively, 3 times a week. Body weights were measured three times a week. At the end, the rats were euthanized and the tongue was removed. Histological evaluations for carcinogenesis were carried out under a light microscope. Results. The mean body weights of rats in groups B, C and D were significantly lower than that in group A (P < 0.05). There were no significant differences in weight changes between groups B, C and D. In the present study, after 12 weeks of treatment, Tongue specimens in groups B and C did not exhibit severe dysplastic changes; however, concurrent hyperplasia, without atypia and mild-to-moderate dysplastic changes were detected. These changes were significantly less than those in group D, with significant differences between group D and groups A, B and C (P<0.001, P<0.01 and P<0.05, respectively). Conclusion. HESA-A has dose-dependent inhibitory effects on the development of neoplasms of the tongue.