Role and clinical significance of RLIP76 in regulation of multi-drug resistance of small cell lung cancer.
- Author:
Pan HAIXIA
;
Bai YIFENG
;
Hu HONGLIN
- Publication Type:Journal Article
- MeSH: ATP-Binding Cassette Transporters; metabolism; physiology; Antineoplastic Agents; pharmacology; Cisplatin; pharmacology; Down-Regulation; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Etoposide; pharmacology; GTPase-Activating Proteins; metabolism; physiology; Humans; Lung Neoplasms; drug therapy; metabolism; RNA, Small Interfering; Real-Time Polymerase Chain Reaction; Small Cell Lung Carcinoma; drug therapy; metabolism; Transfection; Up-Regulation
- From: Chinese Journal of Oncology 2015;37(4):266-271
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo investigate the role of RLIP76 in regulating multi-drug resistance in small cell lung cancer (SCLC), and to analyze the relationship between its expression and prognosis.
METHODSThe expressions of RLIP76 protein and gene were detected by Western blotting and real-time PCR (RT-PCR) in both the chemosensitive SCLC H69 cell line and chemoresistant H69AR cell line, respectively. siRNA was transfected into the H69AR cells to inhibit RLIP76 expression, and eGFP-RLIP76 was transfected into the H69 cells to enhance RLIP76 expression. The drug-sensitivity of cells to chemotherapeutic drugs (ADM, DDP, VP-16) were detected by CCK8 assay. The expression of RLIP76 in the SCLC tissues was detected by immunohistochemistry. The relationship of RLIP76 expression with clinicopathological features and prognosis of the patients was analyzed.
RESULTSThe expression of RLIP76 in H69AR cells was 13.675 ± 0.983, significantly higher than 1.074 ± 0.107 in the H69 cells (P < 0.01). The drug-sensitivities of H69AR cells to chemotherapeutic drugs were significantly increased when the expression of RLIP76 was down-regulated (P< 0.001). The sensitivities of H69 cells to chemotherapeutic drugs ADM, DDP and VP-16 were significantly decreased after transfection with eGFP-RLIP76 up-regulating the RLIP76 expression (P = 0.003). The positive expression rates were 61.3% and 9.4% in the SCLC tumor tissues and para-cancerous tissues, respectively (P < 0.01). The expression of RLIP76 was significantly correlated with clinical stage, chemosensitivity and overall survival of the SCLC patients (P < 0.05).
CONCLUSIONSOur results suggest that RLIP76 is involved in the regulation of small cell lung cancer multidrug resistance. RLIP76 may serve as a potential target gene to evaluate the chemosensitivity and clinical prognostic for small cell lung cancer.