Caveolin-1 affects tumor drug resistance in esophageal squamous cell carcinoma by regulating expressions of P-gp and MRP1

Abstract

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.

Identification of spleen tyrosine kinase as a potential therapeutic target for esophageal squamous cell carcinoma using reverse phase protein arrays

“…pancreatic adenocarcinoma [ 18 , 22 ], prostate cancer [ 22 , 23 ], non-small cell lung carcinoma, renal cell carcinoma (RCC) and glioblastoma [ 17 ]. In our study, we found that CAV1 was overexpressed in ESCC cell lines, which was in agreement with previous studies on CAV1 in ESCC [ 24 – 26 ].…”

ABC Transporters and Their Role in the Neoadjuvant Treatment of Esophageal Cancer

“…However, largest study to date failed to observe any prognostic association for immunohistochemically detected ABCC1 protein expression in tumors from ESCC patients ( n = 829) [ 41 ]. Most recently, correlation of ABCC1 and ABCB1 protein expression with that of Caveolin-1 ( CAV1 , 601047) in tumor tissues from ESCC patients ( n = 84) has been observed and CAV1 expression knockdown also decreased transcript levels of both transporters in ECA-109 cell line in vitro [ 151 ], suggesting a potential interplay between membrane proteins with different functions and their putative use as therapeutic targets. In summary, although predictive value of ABCC1 protein expression has been suggested, studies aiming at its prognostic role failed [ 40 , 41 ] and, therefore, other members of the C family and perhaps combinations of more transporters should be followed in the future.…”

Multifaceted Roles of Caveolin-1 in Lung Cancer: A New Investigation Focused on Tumor Occurrence, Development and Therapy

“…A high Cav-1 level has been shown to be associated with drug resistance during the treatment process of numerous cancers such as lung cancer, esophageal cancer [129], colorectal cancer [130] and renal carcinoma [131]. Cav-1 can enhance drug resistance in some NSCLC cell lines.…”