- VernacularTitle:下调Wnt通路活性对非小细胞肺癌细胞株吉非替尼疗效的影响
- Author:
Xia FANG
1
;
Pan GU
;
Cai-cun ZHOU
;
Sheng-xiang REN
;
Ben-fang LUO
;
Yu ZENG
;
Yun-jin WU
;
Yin-min ZHAO
;
Xu-you ZHU
;
Xiang-hua YI
Author Information
- Publication Type:Journal Article
- MeSH: Antineoplastic Agents; administration & dosage; pharmacology; Apoptosis; Carcinoma, Non-Small-Cell Lung; metabolism; pathology; Cell Line, Tumor; Cell Proliferation; Dose-Response Relationship, Drug; Drug Resistance, Neoplasm; Humans; Lung Neoplasms; metabolism; pathology; Mitogen-Activated Protein Kinase 1; metabolism; Mitogen-Activated Protein Kinase 3; metabolism; Phosphorylation; Quinazolines; administration & dosage; pharmacology; Wnt Signaling Pathway; drug effects; beta Catenin; metabolism
- From: Chinese Journal of Pathology 2013;42(7):455-459
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo explore the effect of Wnt signaling suppression on proliferation of non small cell lung cancer to gefitinib, and its related mechanisms.
METHODSPC9 and PC9/AB2 cells of both gefitinib sensitive and resistant were treated with different concentrations of gefitinib, and the proliferation index was measured using CCK8 kit. The members of Wnt signaling pathway were detected by Western blot. Dual luciferase reportor gene assay (TOP Flash) was used to document the transcriptional level of β-catenin. β-catenin siRNA was transfected into PC9/AB2 cells to suppress the Wnt signaling transcription, followed by treatment with different concentrations of gefitinib. Western blot was then used to detect the expression of EGFR and its downstream signaling after inhibit the expression of β-catenin.
RESULTSTreating with different concentrations of gefitinib, the resistance of PC9/AB2 cells to gefitinib was significantly increased (P < 0.05). The members of Wnt signaling expressed at higher level in PC9/AB2 cells than in PC9 cells (t = 24.590, P = 0.000). TOP Flash examination showed that the endogenous transcriptional activity of Wnt signaling was higher in PC9/AB2 cell than that in PC9 cell (t = 4.983, P = 0.008). Compared with the negative control group, apoptotic rate and sensitivity to gefitinib significantly increased in interfered group (P < 0.05). The expression of p-ERK1/2 significantly decreased after Wnt signaling suppression, although other proteins showed no significant alterations.
CONCLUSIONSuppressing the activity of Wnt signaling can partly reverse the celluar resistance to gefitinib in non small cell lung cancer.