Zhang Song, Cao Wenbo, Yue Mingjin, Zheng Naigang, Hu Tao, Yang Shengli, Dong Ziming, Lu Shixin, Mo Saijun
The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
Department of Basic Science of Oncology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan Province, 450001, China.
Tumour Biol. 2016 Jul;37(7):9189-96. doi: 10.1007/s13277-015-4778-z. Epub 2016 Jan 14.
Esophageal squamous cell carcinoma (ESCC) is the most common cancer in China, and multidrug resistance (MDR) remains one of the biggest problems in ESCC chemotherapy. In this study, we aimed to investigate the mechanism of Caveolin-1, an integral membrane protein, on regulating ESCC MDR. First, immunohistochemistry was used to check the protein expression of Caveolin-1, MDR-related protein of P-glycoprotein (P-gp), and multidrug resistance protein 1 (MRP1) in 84 pathologically characterized ESCC tissues, matched adjacent tumor, and adjacent normal-looking tissues. The results showed that Caveolin-1 expression level was elevated in ESCC tissues than that of matched adjacent tumor and adjacent normal-looking tissues (P < 0.05), and the expression of Caveolin-1 has close correlation with P-gp and MRP1 during tumor genesis of ESCC (P = 0.034, P = 0.009, respectively). Then, Caveolin-1 overexpression and knockdown were used to investigate its effect on expressions of P-gp and MRP1 in ESCC cell line Ec9706. The messenger RNA (mRNA) and protein expression levels of P-gp and MRP1 were checked by real-time quantitative reverse transcription-PCR (qRT-PCR) and Western blot (WB). The results showed that Caveolin-1 overexpression significantly promotes the mRNA and protein expression of MRP1 (P < 0.05), while almost has no effect on the mRNA and protein expression of P-gp (P > 0.05); Cavoelin-1 knockdown inhibits the mRNA and protein expressions of both P-gp and MRP1 (P < 0.05). The similar result was found in another ESCC cell line Eca109. So, it is concluded that Caveolin-1 affects ESCC MDR by regulating the expressions of P-gp and MRP1; therefore, it can be taken as a significant marker and target in tumor therapy.
食管鳞状细胞癌（ESCC）是中国最常见的癌症，多药耐药（MDR）仍然是ESCC化疗中最大的问题之一。在本研究中，我们旨在探讨一种整合膜蛋白小窝蛋白-1（Caveolin-1）调节ESCC多药耐药的机制。首先，采用免疫组织化学法检测84例经病理确诊的ESCC组织、配对的癌旁组织及正常外观组织中Caveolin-1、多药耐药相关蛋白P-糖蛋白（P-gp）和多药耐药蛋白1（MRP1）的蛋白表达。结果显示，ESCC组织中Caveolin-1表达水平高于配对的癌旁组织及正常外观组织（P<0.05），且在ESCC肿瘤发生过程中，Caveolin-1的表达与P-gp和MRP1密切相关（分别为P=0.034，P=0.009）。然后，通过小窝蛋白-1过表达和敲低实验，研究其对ESCC细胞系Ec9706中P-gp和MRP1表达的影响。采用实时定量逆转录聚合酶链反应（qRT-PCR）和蛋白质免疫印迹法（WB）检测P-gp和MRP1的信使核糖核酸（mRNA）和蛋白表达水平。结果显示，小窝蛋白-1过表达显著促进MRP1的mRNA和蛋白表达（P<0.05），而对P-gp的mRNA和蛋白表达几乎无影响（P>0.05）；小窝蛋白-1敲低则抑制P-gp和MRP1的mRNA和蛋白表达（P<0.05）。在另一ESCC细胞系Eca109中也得到了类似结果。因此，得出结论：小窝蛋白-1通过调节P-gp和MRP1的表达影响ESCC多药耐药；因此，它可作为肿瘤治疗中的一个重要标志物和靶点。
