Study On The Mechanisms Of Multidrug Resistance In Adenoid Cystic Carcinoma

OBJECTIVESIn this present study, we establish an in vitro resistance model of adenoid cystic carcinoma, detect six multidrug resistance-associated Markers: p53, gstpl, mdrl, bcl-2, mrp and 1rp, studied the expression and clinical significances of the P53, P-glycoprotein (P170), glutathione S-transferase (GST-π), Bcl-2, multidrug resistance-associated protein (MRP) and lung resistance protein (LRP) in orbital adenoid cystic carcinoma. These can provide theoretical information and clinical referance for elucidating the mechanisms of multidrug resistance (MDR), improving the chemotherapy scheme, evaluating the prognosis and reserving the MDR in orbital adenoid cystic carcinoma.METHODS1. The expression of P53, GST-π, P170, Bcl-2, MRP and LRP in 51 cases of orbital adenoid cystic carcinoma and 10 cases of normal orbital tissues were detected by immunohistochemisry analysis.2. The resistance cell line, ACC/VCR, was induced in the ACC cell line in vitro by progressive concentrations of vincristine(VCR), a drug of choice in the treatment of adenoid cystic carcinoma.3. The growth curve ,drug sensitivity in the parental and resistant cell lines were investigated by cell counting, flow cytometry and MTT assay. The expression of p53, gstp1, mdrl and bcl-2 gene were detected by RT-PCR while P53, GST- π , P170 and Bcl-2 protein weredetected by immunohistochemisry analysis.4. The expression of P53> GST- n , P170 and Bcl-2 in 51 cases of orbital adenoid cystic carcinoma and 10 cases of normal orbital tissues were detected by immunohistochemisry analysis.RESULTS1. P53^ GST- it> P170 and Bcl-2 expression percentage were 52. 94%> 1009L 82. 35% and 64. 71% respectively in orbital adenoid cystic carcinoma and were higher than in normal orbital tissues. The positive rate of P53 and P170 expression in adenoid-tubular ACC was higher than in solid ACC. The positive rate of P53 and Bcl-2 expression in recurrent tumor group was higher than in primary tumor group. Significant correlation was found between the expression of P53 and Bcl-2.2. ACC/VCR cell line was cross-resistant to vincristine (VCR), adriamycine (ADM) and pingyangmycin (PYM), but not resistant to Cyclophosphamide (CTX)> fluorouracil (5-FU) and cisplatin (DDP). There was no significant difference in the doubling time and morphological changes between ACC cell line and ACC/VCR cell line.3. In ACC cell line, the expressions of p53 and gstpl mRNA were lower and mdrl and bcl-2 mRNA were undetectable while P53 and GST- n were positive and P170 and Bcl-2 were negative. In ACC/VCR cell line, the expressions of p53x gstpK mdrl and bcl-2 mRNA were relatively higher while P53, GST-n. P170 and Bcl-2 were positive.CONCLUSIONS1. The overexpressions of P53>GST-n ^ PI70 and Bcl-2 were participated...