TGF-α increases neuroendocrine differentiation and strengthens chemoresistance in prostate cancer DU145 cells.
10.3969/j.issn.1672-7347.2013.02.006
- Author:
Jun WANG
1
;
Xiongbing ZU
;
Yuan LI
Author Information
1. Department of Urology, Xiangya Hospital, Central South University, Changsha, China.
- Publication Type:Journal Article
- MeSH:
Antineoplastic Agents;
pharmacology;
Cell Line, Tumor;
Cisplatin;
pharmacology;
Drug Resistance, Neoplasm;
drug effects;
Endosomal Sorting Complexes Required for Transport;
pharmacology;
Humans;
Male;
Prostatic Neoplasms;
metabolism;
pathology;
Transforming Growth Factor alpha;
pharmacology
- From:
Journal of Central South University(Medical Sciences)
2013;38(2):142-147
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To study whether TGF-α possesses similar EGF effect of enforcing neuroendocrine differentiation (NED) in prostate cancer cell line DU145 and determine the influence of NED induced by TGF-α on chemoresistance.
METHODS:DU145 cells were divided into 3 groups: a group with 2% FBS, a group with 2%FBS+TGF-α 5 ng/mL and a group with 2%FBS+TGF-α 10 ng/mL. Morphological change in DU145 cells was observed after TGF-α treatment. Expression levels of NSE mRNA were detected with real time RT-PCR. Western blot was used to detect the expression levels of protein NSE, P-gp, MRP1 and Bcl-2. Cell cycles of DU145 cells in the 3 groups were examined with flow cytometry. MTT assay was used to evaluate the influence of TGF-α in chemoresistance.
RESULTS:Compared with DU145 cells cultured with 2% FBS, cells treated with 2% FBS+TGF-α were pleomorphic and pseudopodia extended. The expression level of NSE mRNA upregulated to (3.6±0.5) folds (P<0.05) and (10.1±0.1) folds (P<0.01). Western blot showed that the expression levels of protein NSE, Bcl-2, and MRP1 increased after treatment with different concentrations of TGF-α; P-gp was not detected. The proportion of DU145 cells in phase G1 decreased; proportions of cells in phase S and phase G2/M were increased after TGF-α treatment (5 μg/mL). At the same time, chemoresistance of DU145 cells to cisplatin increased.
CONCLUSION:TGF-α can increase NED in DU145 cells and enforce the chemoresistance to cisplatin.
