Resistance reverse effect of anemoside B4 and tetrandrine on oxaliplatin-resistant human colon cancer cells and the mechanism

李敏; 方明治

doi:10.3969/j.issn.1007-3969.2015.01.007

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Resistance reverse effect of anemoside B4 and tetrandrine on oxaliplatin-resistant human colon cancer cells and the mechanism

更新时间：2025-12-31

- Resistance reverse effect of anemoside B4 and tetrandrine on oxaliplatin-resistant human colon cancer cells and the mechanism
- China Oncology Vol. 25, Issue 1, Pages: 38-44(2015)
- 作者机构：
  
  南京市中医院肿瘤科,江苏,南京,210001
- 作者简介：
- 基金信息：
- DOI：10.3969/j.issn.1007-3969.2015.01.007
  CLC：
- Published Online：08 May 2015，
  
  Published：08 May 2015
- 稿件说明：
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李敏,方明治. 白头翁皂苷B4、粉防己碱对奥沙利铂耐药的结肠癌细胞的耐药逆转作用及其机制[J]. 中国癌症杂志, 2015, 25(1): 38-44.

李敏, 方明治. Resistance reverse effect of anemoside B4 and tetrandrine on oxaliplatin-resistant human colon cancer cells and the mechanism[J]. China Oncology, 2015, 25(1): 38-44.
李敏,方明治. 白头翁皂苷B4、粉防己碱对奥沙利铂耐药的结肠癌细胞的耐药逆转作用及其机制[J]. 中国癌症杂志, 2015, 25(1): 38-44. DOI： 10.3969/j.issn.1007-3969.2015.01.007.

李敏, 方明治. Resistance reverse effect of anemoside B4 and tetrandrine on oxaliplatin-resistant human colon cancer cells and the mechanism[J]. China Oncology, 2015, 25(1): 38-44. DOI： 10.3969/j.issn.1007-3969.2015.01.007.

摘要

背景与目的：奥沙利铂(oraliplatin，L-OHP)是结直肠癌最常用的化疗药物之一，但临床上常见结直肠癌L-OHP化疗耐药。本研究旨在探讨中药单体白头翁皂苷B4(anemoside B4，AB4)以及粉防己碱(Tetrandrine，Tet)对人结肠癌L-OHP耐药细胞LoVo/L-OHP耐药的逆转作用，并初步研究其机制。方法：采用浓度梯度实验筛选无毒剂量的AB4、Tet，无毒剂量的AB4、Tet作用于LoVo/L-OHP细胞48 h后，检测LoVo/L-OHP细胞对L-OHP耐药的变化，检测处理后细胞凋亡、细胞周期变化情况，通过RT-PCR及Western blot检测相关基因P-gp、zDHHC9和SMAD4的mRNA及蛋白的表达水平。结果：AB4及Tet作用48 h后对LoVo/L-OHP细胞的5%抑制率浓度分别为0.71及0.45 μg/mL，以此作为无毒剂量。L-OHP对LoVo/L-OHP细胞IC50为(112.5±23.6)μg/mL，分别加入0.71 μg/mL AB4及0.45 μg/mL Tet后，L-OHP对LoVo/L-OHP细胞的IC50值分别为 (62.8±21.4)及(58.9±26.3) μg/mL，IC50值均显著下降(P值均0.05)。细胞周期检测发现，AB4及Tet处理后G1期细胞略有减少，S期细胞略有增加，但差异无统计学意义(P0.05)。细胞凋亡检测发现AB4及Tet处理后凋亡率略有上升，但差异均无统计学意义(P0.05)。RT-PCR检测显示耐药细胞相对于亲本细胞，P-gp及zDHHC9基因表达升高，SMAD4表达降低(P值均0.05)，经过AB4处理后，耐药细胞P-gp基因表达下降。Western blot检测相关蛋白水平后发现，耐药细胞经过AB4处理后，P-gp蛋白表达下降，经过Tet处理后zDHHC9蛋白表达下调。结论：AB4及Tet能逆转LoVo/L-OHP耐药细胞对L-OHP的耐药，AB4逆转机制可能与降低P-gp表达有关，Tet逆转机制与降低zDHHC9表达水平有关。

Abstract

Background and purpose: Oxaliplatin (L-OHP) is one of the most commonly used chemotherapy drugs in colorectal cancer and L-OHP-resistance is very common in colorectal cancer therapy. This research was to discuss the reversal effect in L-OHP-resistant human colon cancer cell line LoVo/L-OHP by anemoside B4 (AB4) and tetrandrine (Tet) and to clarify their molecular mechanism. Methods: LoVo/L-OHP cells were treated for 48 h by AB4 and Tet at different concentrations to get non-toxic dose. Drug sensitivity was measured by MTT. After the treatment

the cell cycle and apoptosis of the cells were detected. Expression of P-gp mRNA

zDHHC9 mRNA and SMAD4 mRNA were detected by RT-PCR. Expression of P-gp

zDHHC9 and SMAD4 protein were detected by Western blot. Results: The IC50 of LoVo/L-OHP for L-OHP was (112.5±23.6) μg/mL

and the IC50 decreased to (62.8±21.4) μg/mL (P0.05) and (58.9±26.3) μg/mL (P0.05) after the treatment with 0.71 μg/mL AB4 and 0.45 μg/mL Tet (non-toxic dose) separately. The cell cycle experiment showed that the cells in G1 stage decreased and in S stage increased but with no statistical significance (P0.05). The cell apoptosis experiment showed that the apoptotic rate increased after the treatment with AB4 and Tet with non-toxic dose but with no statistical significance (P0.05). The RT-PCR experiment showed that the expressions of P-gp mRNA and zDHHC9 mRNA were increased and SMAD4 mRNA was decreased in LoVo/L-OHP cells compared with in LoVo cells (P0.05)

while it was found that P-gp mRNA in LoVo/L-OHP cells was decreased after the treatment with AB4 at non-toxic dose (P0.05). Western blot experiment showed the protein of P-gp in LoVo/L-OHP cells was decreased after treatment with AB4 (P0.05)

which was accordant to the PCR result. The expression of zDHHC9 protein in LoVo/L-OHP cells was decreased in LoVo/L-OHP cells after treatment with Tet (P0.05). Conclusion: AB4 and Tet have some reversal effect on resistant to L-OHP in LoVo/L-OHP cells. The molecular mechanism of the resistance reverse effect was related to down-regulation of P-gp for AB4 and down-regulation of zDHHC9 for Tet.

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