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.

• Authors: Song Zhang, Wenbo Cao, Mingjin Yue, Naigang Zheng, Tao Hu, Shengli Yang, Ziming Dong, Shixin Lu, Saijun Mo
• Journal: Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine (Tumour Biol) Vol. 37 Issue 7 Pg. 9189-96 (Jul 2016) ISSN: 1423-0380 [Electronic] Netherlands
• PMID: 26768616 (Publication Type: Journal Article)

Chemical References

• ATP Binding Cassette Transporter, Subfamily B
• CAV1 protein, human
• Caveolin 1
• Multidrug Resistance-Associated Proteins
• RNA, Messenger
• multidrug resistance-associated protein 1

Topics

• ATP Binding Cassette Transporter, Subfamily B (genetics)
• Carcinoma, Squamous Cell (genetics)
• Caveolin 1 (genetics)
• Cell Line, Tumor
• Drug Resistance, Neoplasm (genetics)
• Esophageal Neoplasms (genetics)
• Esophageal Squamous Cell Carcinoma
• Female
• Gene Expression Regulation, Neoplastic (genetics)
• Humans
• Male
• Middle Aged
• Multidrug Resistance-Associated Proteins (genetics)
• RNA, Messenger (genetics)