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.

XPC inhibition rescues cisplatin resistance via the Akt/mTOR signaling pathway in A549/DDP lung adenocarcinoma cells

“…The results indicated that the reduced levels of excision repair cross-complementing 1 (ERCC1), xeroderma pigmentosum, complementation group A (XPA) or xeroderma pigmentosum, complementation group F (XPF) were associated with the development and prognosis of lung carcinoma (16). Furthermore, in vitro studies have linked high ERCC1 expression with platinum resistance in several types of cancer, while the detection of ERCC1 has been used as a biomarker for individualized treatment in lung cancer patients (17)(18)(19). A previous study examined the silencing of various NER genes in HeLa cells and demonstrated that the suppression of XPC expression could lead to an increased sensitivity for etoposide treatment combined with DDP (20).…”

Suppression of tumor cell proliferation and migration by human umbilical cord mesenchymal stem cells: A possible role for apoptosis and Wnt signaling

“…Solid tumors are often malignant and are a serious threat to human health. At present, lung carcinoma is the most common type of malignancy and hepatocellular carcinoma (HCC) is the second most common cause of cancer-associated mortality ( 1 , 2 ). Surgical resection followed by radiotherapy and/or chemotherapy remains a common treatment for malignant tumors ( 3 , 4 ).…”

<p>Different Proteins Regulated Apoptosis, Proliferation and Metastasis of Lung Adenocarcinoma After Radiotherapy at Different Time</p>

“…The XWLC-05 cell was a kind of human lung adenocarcinoma cell line, supported by the first No.1 Affiliated Hospital of Kunming Medical University. [7][8][9][10] The A549 cell line (Cell center, Yunnan, China) and XWLC-05 cell line were maintained in RPMI-1640 (HyClone, USA) containing 10% fetal bovine serum (FBS; Gibco, USA). Cells were incubated at 37°C in a humidified incubator with 5% CO 2 and treated with different radiation doses of 4 and 8 Gy.…”