[Resveratrol increases sensitivity of CNE2 cells to chemotherapeutic drugs under hypoxia].
OBJECTIVE
To explore the sensitization effects of resveratrol on CNE2 nasopharyngeal carcinoma cell line with hypoxia-induced chemotherapy resistance and the potential mechanism.


METHODS
Human CNE2 nasopharyngeal carcinoma cell line was cultured under hypoxic conditions (37 degrees centigrade, 5% CO(2), 2% O(2)) in vitro. The cultured cells were treated with different concentrations of resveratrol for 48 h. Reversal fold (RF) of reseratrol to chemotherapeutic drugs in CNE2 cells was measured by methyl thiazolyl tetrazolium (MTT) assay. Apoptotic rate of CNE2 cells was observed by flow cytometry. Reverse transcription-polymerase chain reaction (RT-PCR) method and Western blotting were used to investigate the expressions of multidrug resistance gene 1 (mdr1), multidrug resistance-associated protein 1 (MRP1) and hypoxia inducible factor 1alpha (HIF-1alpha) in CNE2 cells.


RESULTS
Resveratrol combined with chemotherapeutics produced a synergistic effect. The RF of 200 micromol/L resveratrol to paclitaxel was 2.58. Combined with paclitaxel, 25, 50, 100 and 200 micromol/L of resveratrol increased the apoptotic rate of CNE2 cells from (22.14+/-1.09)% to (23.24+/-1.37)%, (27.57+/-2.01)%, and (30.36+/-2.31)%, respectively. Resveratrol could down-regulate the expressions of HIF-1alpha, mdr1 and MRP1 significantly. After being treated with resveratrol at different concentrations separately, the expressions of HIF-1alpha, mdr1 and MRP1 in CNE2 cells decreased significantly as compared with paclitaxel alone or paclitaxel plus verapamil (P<0.01).


CONCLUSIONS
Resveratrol can enhance the sensitivity of CNE2 cells to chemotherapeutic drugs under hypoxia. The potential mechanism is partly attributed to inhibiting the gene expressions of HIF-1alpha, mdr1 and MRP1.
Quan
Fang
F
Department of ENT & Head and Neck Surgery, the First Affiliated Hospital, Xi'an Jiao Tong University, Xi'an 710061, Shaanxi Province, China. quanfang2008@sina.com
Zhang
Shao-Qiang
SQ
Bai
Yan-Xia
YX
Yao
Xiao-Bao
XB
Li
Hong-Hui
HH
Yu
Liang
L
Pan
Cheng-En
CE
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D002277:Carcinoma / Q000473:pathology*; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000187:drug effects; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000187:drug effects; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000187:drug effects; D009303:Nasopharyngeal Neoplasms / Q000473:pathology*; D017239:Paclitaxel / Q000494:pharmacology; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*
D000972:Antineoplastic Agents, Phytogenic; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D017239:Paclitaxel; D000077185:Resveratrol; D013267:Stilbenes; C497442:HIF1A protein, human; C421109:multidrug resistance-associated protein 1