title: Downregulation of caveolin-1 increases the sensitivity of drug-resistant colorectal cancer HCT116 cells to 5-fluorouracil.
abstract: Colorectal cancer is the third most common type of cancer in men and women. Chemotherapy is an important treatment strategy for patients with terminal stage cancer. However, the development of drug resistance hampers the effectiveness of chemotherapy. Therefore, an effective therapeutic approach to target chemoresistance-associated cellular molecules is required. In the present study, drug-resistant human colorectal cancer HCT116 cells were developed by treating HCT116 cells with increasing concentrations of 5-fluorouracil (5-FU). The present study indicated that the drug-resistance cells (DRC) were resistant to 5-FU compared with parental HCT116 cells by detecting cell survival using an MTT assay. Additionally, the expression of the chemoresistance-associated protein caveolin-1 (Cav-1) was assessed by reverse transcription-quantitative polymerase chain reaction and western blotting. The results revealed that the Cav-1 expression level was significantly higher in DRC compared with that in the parental HCT116 cells. Next, Cav-1 was silenced by small interfering RNA (siRNA) or was inhibited with its specific inhibitor methyl β-cyclodextrin (MCD). MTT assay demonstrated that Cav-1 siRNA and MCD resensitized DRC to 5-FU. These data reveal that Cav-1 was involved in the development of resistance, suggesting that Cav-1 is a potential target for the treatment of colorectal cancer chemoresistance. In addition, 5-FU combined with Cav-1 siRNA or its specific inhibitor may increase the effectiveness of the treatment strategy.
authors.affiliation: Department of Oncology, Affiliated Hospital of Hangzhou Normal University, Hangzhou, Zhejiang 310015, P.R. China.
authors.forename: Zhaoyang
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Ultrasound, Affiliated Hospital of Hangzhou Normal University, Hangzhou, Zhejiang 310015, P.R. China.
authors.forename: Ning
authors.initials: N
authors.lastname: Wang
authors.affiliation: Department of Oncology, Affiliated Hospital of Hangzhou Normal University, Hangzhou, Zhejiang 310015, P.R. China.
authors.forename: Changxin
authors.initials: C
authors.lastname: Huang
authors.affiliation: Second Clinical College of Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, P.R. China.
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Bao
authors.affiliation: Department of Radiation Oncology, The First People's Hospital of Xiaoshan, Hangzhou, Zhejiang 311200, P.R. China.
authors.forename: Yiqian
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Oncology, Affiliated Hospital of Hangzhou Normal University, Hangzhou, Zhejiang 310015, P.R. China.
authors.forename: Guiting
authors.initials: G
authors.lastname: Zhu
keywords: caveolin-1; colorectal cancer; drug resistant; fluorouracil; survival