title: Cholesterol reduces the sensitivity to platinum-based chemotherapy via upregulating ABCG2 in lung adenocarcinoma.
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.
authors.affiliation: Department of Internal Medicine, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, Henan, 450008, PR China.
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Clinical Laboratory Medicine, Shanghai Tenth People's Hospital of Tongji University, Shanghai, 20072, PR China.
authors.forename: Ruirui
authors.initials: R
authors.lastname: Si
authors.affiliation: Department of Internal Medicine, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, Henan, 450008, PR China.
authors.forename: Hong
authors.initials: H
authors.lastname: Tang
authors.affiliation: Department of Internal Medicine, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, Henan, 450008, PR China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: He
authors.affiliation: Department of Internal Medicine, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, Henan, 450008, PR China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Department of Internal Medicine, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, Henan, 450008, PR China.
authors.forename: Lili
authors.initials: L
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, 25/Ln. 2200 Xietu Road, Shanghai, 200032, PR China.
authors.forename: Yingchao
authors.initials: Y
authors.lastname: Fan
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215006, PR China.
authors.forename: Suhua
authors.initials: S
authors.lastname: Xia
authors.affiliation: Department of Oncology, Changhai Hospital, Second Military Medical University, Shanghai, 200433, PR China.
authors.forename: Zelai
authors.initials: Z
authors.lastname: He
authors.affiliation: Department of Internal Medicine, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, Henan, 450008, PR China. Electronic address: qimingwang1006@126.com.
authors.forename: Qiming
authors.initials: Q
authors.lastname: Wang
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000037:antagonists & inhibitors / Q000235:genetics*; D000230:Adenocarcinoma / Q000097:blood / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D000077192:Adenocarcinoma of Lung; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use; D016190:Carboplatin / Q000008:administration & dosage / Q000627:therapeutic use; D045744:Cell Line, Tumor; D002784:Cholesterol / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D002945:Cisplatin / Q000008:administration & dosage / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D005260:Female; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008175:Lung Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000235:genetics*; D009529:Nicardipine / Q000008:administration & dosage / Q000627:therapeutic use; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000627:therapeutic use*; D000077150:Oxaliplatin; D015854:Up-Regulation
chemical_list: C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D000970:Antineoplastic Agents; D009363:Neoplasm Proteins; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D002784:Cholesterol; D016190:Carboplatin; D009529:Nicardipine; D002945:Cisplatin
keywords: ABCG2; Chemosensitivity; Cholesterol; Lung adenocarcinoma