The expression and significance of MRP1, LRP, TOPOIIß, and BCL2 in tongue squamous cell carcinoma.

BACKGROUND: Multiple drug resistance protein 1 (MRP1), lung resistance protein (LRP), topoisomerase IIß (TOPOIIß) and B-cell lymphoma 2 (BCL2) are well known in the development of drug resistance in cancer cells. The aim of this study was to evaluate the relationship between them and the clinicopathological features, their expression differences between tumor tissue and experimental drug-resistant model in tongue carcinoma. MATERIALS AND METHODS: Multiple drug resistance protein 1, LRP, TOPOIIß, and BCL2 expression was examined by immunohistochemistry in specimens from radical surgeries of 65 patients with tongue carcinoma. A cisplatin-resistance cell line, SCC-15/cisplatin, was established from a cisplatin-sensitive cell line, SCC-15. A MTT-based method was used to analyze drug potencies. Immunofluorescence was used to detect protein expression in both cell lines. Western blot was used to compare the protein expressions in specimens and SCC-15/cisplatin cells. RESULTS: We found higher expression of MRP1, LRP, and BCL2 and lower expression of TOPOIIß in tongue carcinoma compared with adjacent non-neoplastic tongue tissues (P < 0.05). In addition, MRP1 and TopoIIß expression were significantly associated with clinical stage, lymph node metastasis and histologic grade, and LRP was significantly associated with histologic grade in the samples (P < 0.05). Finally, Western blot showed that higher expressions of MRP1, LRP, and BCL2 and lower expression of TopoIIß were observed in SCC-15/cisplatin cells than in clinical samples. CONCLUSION: Our results suggest that the high expressions of MRP1, LRP, and BCL2 and low expression of TOPOIIß in patients with tongue carcinoma indicates that intrinsic drug resistance may exist in tongue carcinoma, and is associated with tumor differentiation and cisplatin resistance in tongue carcinoma.

[Radiation-inducible promoters-mediated cdglytk gene in the treatment of buccal carcinoma in golden hamster].

OBJECTIVE: To observe the therapeutic effect of CDglyTK gene mediated by radiation-inducible promoters in the treatment of buccal carcinoma in Golden Hamster. METHODS: Animal models of buccal carcinoma in golden hamster were established by painting 0.5% dimethyl-benzanthracene. The plasmids pcDNA (+) 3.1/E-CDglyTK were transfected into tumors by lipofectamine. 24 h later, the tumors were exposed to 3 Gy irradiation. Animals were monitored at regular intervals for volume of tumors. CDglyTK mRNA was assayed by RT-PCR. Apoptosis and proliferating cell nuclear antigen were detected respectively by in situ end-labeling and immunohistochemical methods. RESULTS: Compared with control groups, the tumor was suppressed obviously by CDglyTK gene therapy combined with 3 Gy induction radiation. The expression of CDglyTK gene could be detected by RT-PCR in the transfected tumor, and up-regulation of CDglyTK expression was found in tumor exposed to radiation (P < 0.05). There was significant difference in apoptosis index or proliferation index between tumor without irradiation and tumor with irradiation (P < 0.05). CONCLUSIONS: The radiation-inducible promoter can be served as a molecular switch to regulate the expression of CDglyTK gene in buccal carcinoma in golden hamster, and low dose induction radiation can significantly improve the therapeutic effects.

[Interaction of vascular endothelial growth factor-C over-expression with tongue squamous cell carcinoma cell line Tca8113 with peri-carcinoma lymphatics].

OBJECTIVE: To detect the role of Vascular endothelial growth factor C (VEGF-C) in the interaction of tongue squamous cell carcinoma (TSCC) with the peri-carcinoma lymphatics. METHODS: TSCC cells were implanted on the chorioallantoic membrane (CAM), in which, group A was transfected by plasmid pREP7 including VEGF-C, group B was transfected by plasmid pREP7, and group C was Tca8113. Lymphatic vessels were stained by 5'-Nase. Morphologic analysis was used to evaluate the alteration of lymphatic vessels density (LVD), area and perimeter. RESULTS: The transplanted tumor well on CAM. The expression of VEGF-C in group A was higher than that in control group B and C. The LVD, perimeter and area in group A were (5.3 +/- 0.41)/high-power field, (148 +/- 21) microm and (76.8 +/- 13.5) microm(2) respectively in group A, which were significantly higher than that of group B and C (P < 0.01), while there were no significant difference between group B and C. CONCLUSIONS: CAM is ideal model for the research of lymphatic vessels; Over-expression of VEGF-C could induce the dilatation and LVD increase of peri-tumor lymphatic vessels, which maybe one of the mechanisms that VEGF-C metastasis of TSCC through lymphatic vessels.