Study Of DrzE Targeting Folrl Enhance The Sensitivity To Paclitaxel In Nasopharyngeal Carcinoma Transplanted Tumor

Objectives:To study the change of paclitaxel sensitivity in resistant NPC subcutaneously transplanted tumor after using deoxyribozyme DrzE whose targeting folrl gene. And to test the change of the expression of folrl gene.Methods:Culture the human NPC cell line CNE-1and the taxol-resistant sub-line CNE-1/taxol. Establish a nude mice subcutaneously NPC transplanted tumor model. Observe the inhibition of NPC transplanted tumors present situation after the DrzE targeting folrl alone, paclitaxel alone and DrzE-paclitaxel joint application. Study whether DrzE can increase the paclitaxel sensitivity in resistant NPC subcutaneously transplanted tumor. Detecting the change of the expression of folrl gene before and after the treatment of DrzE.Statistical processing:data was expressed by the way of "Mean±SD", according to statistical methods of F test and two sample t test, and defined statistical significance as P<0.05.Results:1. In the establishment of CNE-1and CNE-1/taxol transplanted tumor models, there was a low tumor formation rate (56%) with a latency and a long time(45days) to formate a tumer when using a cell suspension inoculation and a high tumor formation rate (100%) with no latency and a short time(14days) to formate a tumer when using a tissue explant method.2. CNE-1tumor grew faster than CNE-1/taxol tumor, the volome of the CNE-1tumor was80.13±24.50mm3before treatment, while the volome of CNE-1/taxol was59.10±18.72mm3, with a statistically significant difference(P<0.05).3. Paclitaxel alone for NPC CNE-1transplanted tumor can suppress the growth of tumors, but not for CNE-1/taxol tumor; DrzE alone can suppress the growths of both CNE-1and CNE-1/taxol tumor, and more effective to CNE-1/taxol tumor; DrzE-paclitaxel joint application can suppress most effective in the growth of both two planted tumors compare among DrzE alone or paclitaxel alone.4. PCR method to detect folrl expression:the expression of folrl in CNE-1/taxol transplanted tumor was12.47±0.49fold to CNE-1’s bofore treatment. After treatment by the DrzE, the expression of folrl were declined in the DrzE-paclitaxel joint application group and the DrzE alone group. There was each one peak on the folrl and β-actin’s solubility curve, meaning that the gene product was specific and no impurity interference.Conclusions:1. NPC CNE-1transplanted tumors grew faster than CNE-1/taxol tumors.2. The targeting folrl DrzE could transfect successfully within transplanted tumors in nude mice and suppress the growths of both CNE-1and CNE-1/taxol tumors.3. After the treatment by DrzE, the sensitivity of CNE-1/taxol transplanted tumors to paclitaxel was significantly enhanced.