主 办:北 京 中 医 药 大 学
ISSN 1006-2157 CN 11-3574/R

北京中医药大学学报 ›› 2020, Vol. 43 ›› Issue (10): 834-840.doi: 10.3969/j.issn.1006-2157.2020.10.007

• 中药药理 • 上一篇    下一篇

复方浙贝浸膏对人结肠癌耐奥沙利铂细胞株HCT-116/L-OHP裸鼠移植瘤及凋亡蛋白表达的影响*

吕鹏1,2, 董青1, 刘宇1, 李蕊白1, 范秋月1, 陈信义1, 侯丽1#   

  1. 1 北京中医药大学东直门医院 北京 100700;
    2 湖北省恩施土家族苗族自治州中心医院
  • 收稿日期:2019-12-20 出版日期:2020-10-30 发布日期:2020-11-04
  • 通讯作者: #侯丽,女,博士,主任医师,博士生导师,主要研究方向:中西医结合防治恶性肿瘤,E-mail:houli1203@126.com
  • 作者简介:吕鹏,男,博士
  • 基金资助:
    *北京市科技计划“十病十药研发”项目(No.Z151100003815027)

Effects of Compound Zhebei Extract (CZBE) on the expression of apoptotic protein and xenograft tumors of human colon cancer oxaliplatin-resistant cells (HCT-116/L-OHP) in nude mice: an experimental study*

Lyu Peng1,2, Dong Qing1, Liu Yu1, Li Ruibai1, Fan Qiuyue1, Chen Xinyi1, Hou Li1#   

  1. 1 Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China;
    2 Central Hospital, Enshi Tujia and Miao Nationality Autonomic Region, Hubei 445000, China
  • Received:2019-12-20 Online:2020-10-30 Published:2020-11-04
  • Contact: Prof. Hou Li, Ph.D, Doctoral supervisor, Dongzhimen Hospital affiliated to Beijing University of traditional Chinese Medicine, No.5, Haiyuncang Road, Dongcheng District, Beijing 100700, E-mail:houli1203@126.com
  • Supported by:
    “Ten Diseases and Ten Drugs Research and Development” project of Beijing Science and Technology Plan (No.Z151100003815027)Ethical review: Experimental Animal Welfare Ethics Committee of Institute of Traditional Chinese Medicine, Chinese Academy of Sciences (No.20181003)

摘要: 目的 观察复方浙贝浸膏(Compound Zhebei Extract,CZBE)对人结肠癌耐奥沙利铂(L-OHP)细胞株(HCT-116/L-OHP)裸鼠移植瘤体内抑制作用,以及对移植瘤细胞相关凋亡蛋白表达的影响。方法 将人结肠癌耐L-OHP细胞HCT-116/L-OHP接种于BALB/c裸鼠右腋前皮下构建结肠癌耐L-OHP移植瘤模型,成模后按随机数字表法将其分成肿瘤模型对照组、阳性药L-OHP组(3 mg/kg)、CZBE高剂量(CZBE 10 g/kg)联合L-OHP组、CZBE中剂量(CZBE 5 g/kg)联合 L-OHP组、CZBE低剂量(CZBE 2.5 g/kg)联合 L-OHP组,分组当天给药。给药方法:CZBE,灌胃,每日1次;L-OHP,3 mg/kg,腹腔注射,隔日1次。连续用药2周。实验结束后处死小鼠,称体重后完整剥离瘤体并称瘤重,计算肿瘤抑制率。将瘤块组织制成切片,通过免疫组化结合ImageProPlus7.0彩色图像分析软件及SPSS 21.0软件,分析CZBE对HCT-116/L-OHP移植瘤细胞凋亡蛋白表达的影响。结果 CZBE各剂量联合L-OHP均能有效抑制HCT-116/L-OHP裸鼠移植瘤体积的增长。CZBE高剂量联合L-OHP组肿瘤抑制率为45.031%,与阳性药L-OHP组比较差异有统计学意义(P<0.05),CZBE中剂量联合L-OHP组肿瘤抑制率为37.669%,复方浙贝浸膏低剂量联合L-OHP组肿瘤抑制率为32.147%,阳性对照L-OHP组的肿瘤抑制率为27.239%,并延长移植瘤裸鼠的生存期。与阳性药L-OHP组相比, CZBE低剂量联合L-OHP组移植瘤细胞B淋巴细胞瘤-2基因(Bcl-2)的累积光密度/面积(IOD/Area)值降低(P<0.05),CZBE中、高剂量联合L-OHP组移植瘤细胞Bcl-2的IOD/Area值降低(P<0.01)。CZBE中剂量联合L-OHP组移植瘤细胞Bcl-2相关x蛋白(Bax)的IOD/Area值升高(P<0.05),CZBE高剂量联合L-OHP组移植瘤细胞Bax的IOD/Area值升高(P<0.01)。结论 CZBE联合L-OHP能提高人结肠癌耐L-OHP细胞株移植瘤的肿瘤抑制率,并延长人结肠癌耐奥沙利铂移植瘤裸鼠的生存期,其机制可能是通过调节Bax/Bcl-2凋亡途径逆转肿瘤多药耐药性,促进肿瘤细胞凋亡。

关键词: 复发浙贝浸膏, 结肠癌, 奥沙利铂, 多药耐药, HCT-116/L-OHP细胞, 小鼠

Abstract: Objective To observe the inhibitory effect of Compound Zhebei Extract(CZBE) on HCT-116/L-OHP transplanted tumors in nude mice and the expression of apoptotic proteins related to transplanted tumors. Methods HCT-116/L-OHP cells were inoculated into the axilla of BALB/c nude mice to establish L-OHP-resistant transplantation model of colon cancer. After the successful establishment of the model, the transplanted mice were divided into five groups: control group, L-OHP group (3 mg/kg), high-dose CZBE (10 g/kg) combined with L-OHP group, mid-dose CZBE (5 g/kg) combined with L-OHP group, and low-dose CZBE (2.5 g/kg) combined with L-OHP group. Method of administration: CZBE, intragastric administration, once a day; L-OHP, 3 mg/kg, intraperitoneal injection, once every other day for 2 consecutive weeks. At the end of the experiment, the mice were sacrificed and weighed, and then the tumors were removed completely and weighed to calculate the tumor inhibition rate. The tumors were sliced and photographed. Then the effects of CZBE on apoptotic protein expression of HCT-116/L-OHP transplanted tumors were analyzed by using ImageProPlus 7.0 and SPSS21 software. Results CZBE combined with L-OHP could effectively inhibit the growth of HCT-116/L-OHP transplanted tumors in nude mice. The inhibition rate of high-dose CZBE combined with L-OHP group was 45.031%, which was significantly different from that of L-OHP group (P<0.05). The inhibition rate of mid-dose CZBE combined with L-OHP group was 37.669%. The inhibition rate of low-dose CZBE combined with L-OHP group was 32.147%. The inhibition rate of L-OHP group was 27.239% in the positive control group, and the survival time of transplanted nude mice was prolonged. Compared with L-OHP group, IOD/Area of Bcl-2 cells in low-dose CZBE combined with L-OHP group decreased(P<0.05), while IOD/Area of Bcl-2 cells in mid-dose and high-dose CZBE combined with L-OHP group decreased significantly (P<0.01). IOD/Area values of Bax in mid-dose CZBE combined with L-OHP group increased (P<0.05), while IOD/Area values of Bax in high-dose CZBE combined with L-OHP group increased significantly (P<0.01). Conclusion CZBE combined with L-OHP can improve the tumor inhibition rate of L-OHP-resistant human colon cancer cell lines and prolong the survival time of Oxaliplatin-resistant nude mice. The mechanism may be to reverse multidrug resistance and promote apoptosis of tumor cells by regulating Bax/Bcl-2 apoptotic pathway.

Key words: Compound Zhebei Extract, colon cancer, L-OHP, multidrug resistance, HCT-116/L-OHP cell, mice

中图分类号: 

  • R285.5