Effect of Curcumin in Reversing Resistance of Human Colon Carcinoma Against Oxaliplatin Cell Line HCT-116/L-OHP

Hao MA; De-song KONG; Min NI; Ze-yan JIANG; Zheng-xin CHEN; Li-bing GU; Zhi-min FAN

doi:10.13422/j.cnki.syfjx.20191223

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Effect of Curcumin in Reversing Resistance of Human Colon Carcinoma Against Oxaliplatin Cell Line HCT-116/L-OHP

Pharmacology | 更新时间：2021-02-09

- Effect of Curcumin in Reversing Resistance of Human Colon Carcinoma Against Oxaliplatin Cell Line HCT-116/L-OHP
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 25, Issue 20, Pages: 63-69(2019)
- 作者机构：
  
  1.南京中医药大学，南京　 210029；
  2.南京中医药大学　第三附属医院，南京　 210001
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20191223
  CLC： R22; R242; R2-031; R285.5
- Received：31 October 2018，
  
  Published Online：04 March 2019，
  
  Published：20 October 2019
- 稿件说明：
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Hao MA, De-song KONG, Min NI, et al. Effect of Curcumin in Reversing Resistance of Human Colon Carcinoma Against Oxaliplatin Cell Line HCT-116/L-OHP[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(20): 63-69.
DOI：

Hao MA, De-song KONG, Min NI, et al. Effect of Curcumin in Reversing Resistance of Human Colon Carcinoma Against Oxaliplatin Cell Line HCT-116/L-OHP[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(20): 63-69. DOI： 10.13422/j.cnki.syfjx.20191223.

摘要

目的：

构建人结肠癌奥沙利铂(oxaliplatin，L-OHP)耐药细胞株HCT-116/L-OHP，观察姜黄素(curcumin，Cur)对其耐药的逆转作用，并探讨其可能的耐药机制。

方法：

采用浓度梯度递增法，逐步提高作用于亲代人结肠癌细胞HCT-116的L-OHP浓度，建立耐L-OHP的细胞株HCT-116/L-OHP；通过cell counting kit-8(CCK-8)法检测L-OHP和Cur对HCT-116以及HCT-116/L-OHP细胞的细胞毒性，观察Cur能否逆转耐药；蛋白免疫印迹法(Western blot)检测耐药相关蛋白的表达，实时荧光定量聚合酶链式反应(Real-time PCR)检测相关mRNA的改变。

结果：

成功建立了耐L-OHP的人结肠癌耐药细胞株并命名为HCT-116/L-OHP，其耐药指数为12.6。与HCT-116细胞株比较，HCT-116/L-OHP细胞株中切除修复交叉互补基因1(ERCC1)蛋白及mRNA表达水平显著上升(

0.01)，B淋巴细胞瘤-2(B-cell lymphoma-2，Bcl-2)，谷胱甘肽-巯基-转移酶-π(glutathione-s-transferase-π，GST-π)，多药耐药相关蛋白(multidrug resistance-associated protein

MRP)，P-糖蛋白(P-glycoprotein，P-gp)，凋亡抑制基因(Survivin)的表达亦显著上升(

0.01)；不同浓度姜黄素(5，10，20，30，40 μmol·L

－1

)作用后，ERCC1表达下降(

0.01)，Bcl-2，GST-π，MRP，P-gp，Survivin表达也有不同程度下降(

0.05)。

结论：

HCT-116/L-OHP细胞株具有稳定的耐药性，其耐药机制可能为ERCC1的表达上调，而导致Bcl-2，GST-π，MRP，P-gp，Survivin等相关蛋白表达上调，使肿瘤细胞获得耐药性。姜黄素对HCT-116/L-OHP的耐药性具有逆转作用，其作用机制可能是通过降低ERCC1的表达，从而下调Bcl-2，GST-π，MRP，P-gp，Survivin等耐药相关mRNA及蛋白的表达，增加肿瘤对L-OHP的敏感性，从而逆转肿瘤细胞的耐药。

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 (

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 (

0.01). After the treatment with different concentrations of curcumin (5

40 μmol·L

-1

)

the expression of ERCC1 decreased (

0.01)

and the expressions of Bcl-2

GST-π

MRP

P-gp

Survivin also decreased to different degrees (

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-

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.

关键词

Keywords

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