乳源免疫调节肽通过泛素-蛋白酶体途径抑制卵巢癌耐药性及其机制研究  

Immunomodulating peptide inhibits the drug resistance of ovarian cancer cell through the ubiquitin-proteasome pathway

作　　者：阮昕 汪慎燚 徐恰 席浩 薛绍礼[1,2] 秦宜德 Ruan Xin;Wang Shenyi;Xu Qia(Dept of Biochemistry and Molecular Biology,Anhui Medical University,Hefei 23003)

机构地区：[1]安徽医科大学基础医学院生物化学与分子生物学教研室,合肥230032 [2]安徽医科大学生命科学学院生物工程教研室,合肥230032

出　　处：《安徽医科大学学报》2018年第7期989-993,共5页Acta Universitatis Medicinalis Anhui

基　　金：国家自然科学基金(编号:81472448);安徽省自然科学基金(编号:1508085MH196)

摘　　要：目的研究乳源免疫调节肽(PGPIPN)抑制卵巢癌耐药性及其机制。方法 MTT法检测PGPIPN与抗癌药顺铂(DDP)联合用药抑制人卵巢癌敏感细胞株(SKOV_3)、耐药细胞株(SKOV_3-DDP)和原代卵巢癌细胞的半数抑制浓度(IC_(50))和细胞增殖抑制率,PCR法和Western blot法检测人卵巢癌细胞株和原代卵巢癌细胞用药情况下泛素-蛋白酶体途径相关基因的表达。结果 PGPIPN和DDP联合用药细胞增殖抑制率显著高于单独DDP组或PGPIPN组,差异有统计学意义(P<0.05),PCR和Western blot结果表明PGPIPN通过调节泛素-蛋白酶体途径相关基因表达降低卵巢癌细胞的耐药性。PGPIPN促进SIAH和PSMA1表达,降低β-catenin基因的表达(P<0.05,P<0.01),且有剂量依赖性。结论 PGPIPN通过泛素-蛋白酶体途径降低卵巢癌细胞对DDP的耐药性。Objective To study the inhibitory effect of immunomodulating peptide（PGPIPN） on the drug resistance and its mechanism in ovarian cancer.Methods The IC_（50） and cell proliferation inhibition rates were detected in human ovarian cancer cell lines（both sensitive cell line,SKOV3,and drug-resistant cell line,SKOV3-DDP）and primary ovarian cancer cell through the combination of the PGPIPN and cisplatin（DDP） by MTT method.The PCR and Western blot were used to detect the expressions of genes related to the ubiquitin-proteasome pathway in human ovarian cancer cell lines and primary ovarian cancer cells.Results The experimental results showed that the proliferation inhibition rate in combined drug group was higher than that in the groups treated only with DDP and PGPIPN and the difference was statistically significant（P0.05）.The results of PCR and Western blot indicated that PGPIPN lessened the resistance of ovarian cancer cells to DDP by regulating the expressions of genes related to the ubiquitin-proteasome pathway in human ovarian cancer cell lines and primary ovarian cancer cells.PGPIPN promoted the expression of SIAH and PSMA1 genes and reduced the expression of β-catenin gene（P0.05,P0.01） with a dose-dependent manner.Conclusion PGPIPN reduces the resistance of ovarian cancer cells to DDP through the ubiquitin proteasome pathway.

关 键 词：卵巢癌 乳源免疫调节肽 顺铂 泛素-蛋白酶体途径 

分 类 号：R737.31[医药卫生—肿瘤] R979.1[医药卫生—临床医学]