Mechanisms of curcumin to reverse herceptin resistance in gastric cancer cells
10.16438/j.0513-4870.2018-0651
- VernacularTitle:姜黄素逆转胃癌细胞赫赛汀耐药机制研究
- Author:
Wen-hu LIU
1
;
Jiang-bei YUAN
2
;
Lan YANG
1
;
Jin-xia CHANG
3
Author Information
1. School of Pharmacy, North Sichuan Medical College, Nanchong 637100, China
2. School of Pharmaceutical Sciences, Chongqing University, Chongqing 401331, China
3. Innovative Platform of Basic Medical Sciences, School of Basic Medical Sciences, North Sichuan Medical College, Nanchong 637100, China
- Publication Type:ORIGINAL ARTICLES
- Keywords:
curcumin;
gastric cancer;
trastuzumab resistance;
NF-κB signaling pathway;
apoptosis
- From:
Acta Pharmaceutica Sinica
2018;53(11):1817-1824
- CountryChina
- Language:Chinese
-
Abstract:
This study is aimed to investigate the potential mechanisms of herceptin-acquired resistance and curcumin to reverse resistance in NCI N87/R gastric cancer cells. Western blot was used to evaluate the effect of curcumin on the expression of IκBα, NF-κBp65, HER-2, caspase-3, Bcl-2 and Bax in herceptin resistant cells; Annexin V-FITC/PI was exploited to analyze the effect of curcumin on cell apoptosis; Caspase kit was used to evaluate the effect of curcumin on the enzymatic activity of caspase-3, 8 and 9. The results showed a low expression of IκBα in the cytoplasm and a high expression of NF-κBp65 in the nucleus of NCI N87/R cells. Correspondingly, inhibition of NF-κB pathway by EVP4593, a specific NF-κB inhibitor, preferentially reduced cell viability of NCI N87/R cells, indicating the activation of NF-κB pathway in NCI N87/R cells. Curcumin preferentially reduced cell proliferation and inhibited NF-κB signaling pathway of NCI N87/R cells, downregulated the expression of HER-2 and Bcl-2, upregulated the expression of Bax, increased the activity of caspase-3, 8 and 9. Taken together, our study demonstrates the correlation between herceptin resistance acquirement of NCI N87 cells and the activation of NF-κB pathway. Moreover, curcumin reverses herceptin resistance of NCI N87 cells possibly by inhibiting NF-κB pathway and inducing cell apoptosis.
