1. Cholesterol reduces the sensitivity to platinum-based chemotherapy via upregulating ABCG2 in lung adenocarcinoma.
- Author
-
Wu Y, Si R, Tang H, He Z, Zhu H, Wang L, Fan Y, Xia S, He Z, and Wang Q
- Subjects
- ATP Binding Cassette Transporter, Subfamily G, Member 2, ATP-Binding Cassette Transporters antagonists & inhibitors, Adenocarcinoma blood, Adenocarcinoma genetics, Adenocarcinoma metabolism, Adenocarcinoma of Lung, Aged, Antineoplastic Agents administration & dosage, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Carboplatin administration & dosage, Carboplatin therapeutic use, Cell Line, Tumor, Cholesterol administration & dosage, Cholesterol blood, Cisplatin administration & dosage, Female, Humans, Lung drug effects, Lung metabolism, Lung Neoplasms blood, Lung Neoplasms genetics, Lung Neoplasms metabolism, Male, Middle Aged, Neoplasm Proteins antagonists & inhibitors, Nicardipine administration & dosage, Nicardipine therapeutic use, Organoplatinum Compounds administration & dosage, Oxaliplatin, Up-Regulation, ATP-Binding Cassette Transporters genetics, Adenocarcinoma drug therapy, Antineoplastic Agents therapeutic use, Cholesterol metabolism, Cisplatin therapeutic use, Drug Resistance, Neoplasm drug effects, Lung Neoplasms drug therapy, Neoplasm Proteins genetics, Organoplatinum Compounds therapeutic use
- Abstract
Inoperable lung adenocarcinoma is currently treated with platinum-based chemotherapy. However, the effectiveness of these chemotherapeutic agents is not the same for all patients. Patients either show quick chemoresistance (QCR) or delayed chemoresistance (DCR), which are defined by 87 and 242 days of progression-free survival (PFS) after initial platinum-based treatment, respectively. We found that QCR patients displayed an elevated level of serum cholesterol and that their tumors showed upregulated ABCG2 expression. We propose that chemoresistance may be attributed to cholesterol-induced ABCG2 expression and hypothesize that blocking ABCG2 may increase the efficacy of platinum-based chemotherapeutic agents. Using the MTT cell viability assay, we observed that cotreatment with ABCG2 blocker Nicardipine and platinum-based drugs Cisplatin, Oxaliplatin or Carboplatin significantly decreased cell viability of tumor cells. Importantly, our results also showed that incubating cells with cholesterol prior to chemotherapy treatment or cotreatment increased cell viability of tumor cells relative to the controls., (Copyright © 2015 Elsevier Inc. All rights reserved.)
- Published
- 2015
- Full Text
- View/download PDF