title: Chemosensitizing effect of shRNA-mediated ERCC1 silencing on a Xuanwei lung adenocarcinoma cell line and its clinical significance.
abstract: Lung cancer is a common fatal malignancy in both men and women. Xuanwei, Yunnan has the highest incidence of lung cancer in China. The area has a specific risk factor in the domestic combustion of bituminous coal, and lung cancer patients from this area tend to be resistant to platinum-based treatments. However, little is known about the mechanism of platinum resistance in patients from Xuanwei. Herein, we used lentiviral infection with shRNA to silence expression of the DNA repair enzyme ERCC1 in XWLC05 both in its RNA and protein expression level, a lung adenoma cell line derived from a patient from Xuanwei. ERCC1 expression in this cell line is high and contributes to its resistance to cisplatin. Suppression of ERCC1 decreased XWLC05 proliferation in vitro (IC50 of cisplatin 1.34 µM for shRNA-infected cells vs. 4.54 µM for control cells) and increased the apoptotic rate after treatment with cisplatin (81.2% shRNA cells vs. 58% control cells, P<0.05). Progression-free survival was longer in ERCC1-negative lung adenoma patients than those with high ERCC1 levels (30 vs. 11 months, P<0.0001). ERCC1 expression was identified as a prognostic marker for overall survival in the patient cohort with operable lesions. Taken together, our data identify ERCC1 as a disease marker in lung adenoma patients from Xuanwei and confirm the significance of resection for the subsequent effect of platinum treatment in these patients. Additional studies are needed to determine the mechanism of ERCC1-induced platinum resistance in lung adenoma patients from Xuanwei.
authors.affiliation: Department of Chest Surgery, The Third Affiliated Hospital of Kunming Medical University (Tumor Hospital of Yunnan Province), Kunming, Yunnan 650031, P.R. China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of General Surgery, Ganmei Affiliated Hospital of Kunming Medical University (The First People's Hospital of Kunming), Kunming, Yunnan 650032, P.R. China.
authors.forename: Lijun
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, P.R. China.
authors.forename: Liang
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Oncology, Renming Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Yongfa
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Department of Chest Surgery, The Third Affiliated Hospital of Kunming Medical University (Tumor Hospital of Yunnan Province), Kunming, Yunnan 650031, P.R. China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Oncology, Kunming Medical University, Kunming, Yunnan 650031, P.R. China.
authors.forename: Siyuan
authors.initials: S
authors.lastname: Yang
authors.affiliation: Department of General Surgery, Minhang Hospital, Fudan University, Shanghai 201199, P.R. China.
authors.forename: Rongliang
authors.initials: R
authors.lastname: Shi
authors.affiliation: Department of Oncology, Kunming Medical University, Kunming, Yunnan 650031, P.R. China.
authors.forename: Shaojia
authors.initials: S
authors.lastname: Wang
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D000077192:Adenocarcinoma of Lung; D000368:Aged; D000818:Animals; D045744:Cell Line, Tumor; D002681:China; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*; D018572:Disease-Free Survival; D004720:Endonucleases / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D020868:Gene Silencing; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D008297:Male; D051379:Mice; D008875:Middle Aged; D034741:RNA, Small Interfering / Q000235:genetics / Q000627:therapeutic use; D023041:Xenograft Model Antitumor Assays
chemical_list: D004268:DNA-Binding Proteins; D034741:RNA, Small Interfering; C071447:ERCC1 protein, human; D004720:Endonucleases; D002945:Cisplatin