Effect of Curcumin in Reversing Resistance of Human Colon Carcinoma Against Oxaliplatin Cell Line HCT-116/L-OHP
10.13422/j.cnki.syfjx.20191223
- VernacularTitle: 姜黄素逆转人结肠癌耐奥沙利铂细胞株HCT-116/L-OHP的耐药性
- Author:
Hao MA
1
;
De-song KONG
2
;
Min NI
2
;
Ze-yan JIANG
1
;
Zheng-xin CHEN
1
;
Li-bing GU
1
;
Zhi-min FAN
2
Author Information
1. Nanjing University of Chinese Medicine, Nanjing 210029, China
2. The Third Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210001, China
- Publication Type:Research Article
- Keywords:
colorectal neoplasms;
drug resistance;
oxaliplatin;
curcumin;
cell;
HCT-116
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2019;25(20):63-69
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To construct oxaliplatin (L-OHP) drug-resistant cell line HCT-116/L-OHP in human colon cancer, in order to observe the reversal effect of curcumin (cur) on its drug resistance, and preliminarily explore the possible drug resistance mechanism. Method:The concentration gradient increasing method was used to gradually increase the L-OHP concentration of HCT-116 in parental colon cancer cells, and the cell line HCT-116/L-OHP resistant to L-OHP was established. The cytotoxicity of L-OHP and curcumin to HCT-116 and HCT-116/L-OHP cells was detected by cell counting kit-8(CCK-8) method to observe whether curative resistance could be reversed. Western blot was used to detect the expressions of drug-resistance-related proteins. Real-time PCR was used to detect changes in related genes. Result:Human colon cancer cell line resistant to L-OHP were successfully established and named as HCT-116/L-OHP, with a drug resistance index of 12.6.Compared with HCT-116 cell lines, the expression levels of resected and repaired cross complementation gene 1 (ERCC1) protein and gene in HCT-116/L-OHP cell lines were significantly increased (P<0.01). The expressions of B-cell lymphoma-2 (Bcl-2), glutathione-s-transferase-consciousness (GST-consciousness), multidrug resistance-associated protein (MRP), P-glycoprotein (P-gp) and apoptotic inhibitory gene (Survivin) also increased significantly (P<0.01). After the treatment with different concentrations of curcumin (5,10,20,30,40 μmol·L-1), the expression of ERCC1 decreased (P<0.01), and the expressions of Bcl-2,GST-π,MRP,P-gp,Survivin also decreased to different degrees (P<0.05). Conclusion:HCT-116/L-OHP cell lines have a stable drug resistance, and its drug resistance mechanism may be up-regulated with the expression of ERCC1, which leads to the up-regulation of Bcl-2,GST-π,MRP,P-gp,Survivin and other related proteins, and enables tumor cells to acquire drug resistance. Curcumin can reverse the drug resistance of HCT-116/L-OHP, and its mechanism may be to reduce the expression of ERCC1, thereby down-regulating the expressions of Bcl-2,GST-π,MRP,P-gp,Survivin and other drug-resistant related genes and proteins, and increase the sensitivity of tumor to L-OHP, so as to reverse the drug resistance of tumor cells.
