靶向FOLR1的脱氧核酶提高鼻咽癌移植瘤对紫杉醇的敏感性

FOLR1-targeted deoxyribozyme enhanced the sensitivity of nasopharyngeal carcinoma xenografted tumor to paclitaxel

目的:探讨裸鼠鼻咽癌移植瘤能否通过靶向FOLR1的脱氧核酶(DrzE)提高其对紫杉醇的敏感性。方法:取CNE-1鼻咽癌亲本细胞及CNE-1/taxol紫杉醇耐药细胞进行裸鼠成瘤实验,分别予靶向FOLR1的“10-23”型DrzE单用和紫杉醇单用及紫杉醇-DrzE联用后比较各组鼻咽癌移植瘤体的抑制情况。RT-qPCR及Western blot检测用药前后各组瘤体FOLR1 mRNA及蛋白的表达。结果:CNE-1瘤体较CNE-1/taxol瘤体生长速度快,瘤体体积更大(P<0.05);CNE-1瘤体生长能被紫杉醇单药抑制,但紫杉醇对CNE-1/taxol瘤体无效;两种瘤体生长均能被DrzE单药抑制,其中耐药瘤体更显著(P<0.05);紫杉醇与DrzE联用较分别单用两药对移植瘤的抑制作用更显著(P<0.05);给药前CNE-1/taxol移植瘤中FOLR1的表达量显著高于CNE-1(P<0.01),用药后DrzE单药组及紫杉醇与DrzE联用组中两种移植瘤体FOLR1表达量均显著低于对照组(P<0.05)。结论:靶向FOLR1的脱氧核酶DrzE转染裸鼠移植瘤体后可减慢鼻咽癌瘤体的生长,提高鼻咽癌耐药移植瘤体对紫杉醇的敏感性。

Objective:To investigate whether taxol sensitivity of nasopharyngeal carcinoma(NPC)grafts in nude mice could be enhanced by FOLR1-targeted deoxyribozyme(DrzE).Methods:NPC parent cells—CNE-1 cells and paclitaxel-resistant CNE-1/taxol cells were used for tumor formation experiment in nude mice.Then,the inhibition difference of NPC xenografted tumors was compared after receiving FOLR1-targeted DrzE alone and the combination of DrzE and paclitaxel.RT-qPCR and Western blot were used to detect the expression of FOLR1 in tumors before and after treatment.Results:CNE-1 tumors grew faster and larger than CNE-1/taxol transplanted tumors(P<0.05).Paclitaxel alone could inhibit the growth of CNE-1 transplanted tumor,but had no effect on paclitaxel-resistant tumors.Both CNE-1 and CNE-1/taxol transplanted tumors were inhibited by deoxyribozyme DrzE alone,and the inhibitory effect on the paclitaxel-resistant tumors was more significant(P<0.05).The combination of paclitaxel and deoxyribozyme had more significant inhibitory effect on the transplanted tumors than either drug alone(P<0.05).The expression of FOLR1 in CNE-1/taxol transplanted tumor before treatment was significantly higher than that in CNE-1(P<0.01).Meanwhile,the expression of FOLR1 in DrzE group and the DrzE-paclitaxel group was significantly lower after treatment than that in the control group(P<0.05).Conclusion:The transfection of deoxyribozyme DrzE targeting FOLR1 in the transplanted tumor of nude mice can reduce the proliferation rate of nasopharyngeal carcinoma and increase the sensitivity of drugresistant transplanted tumor to paclitaxel。