Zhang Yong, Zhang Qiang, Fan Zhongze, Sun Jue, Liu Xulin, Cheng Lingling, Li Ao, Xu Jianhua
Department of Medical Oncology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Pathol Oncol Res. 2015 Apr;21(2):389-97. doi: 10.1007/s12253-014-9831-5. Epub 2014 Aug 8.
Chang-Wei-Qing (CWQ), a Chinese herbal formula, has long been employed clinically to treat cancers. In this study, we investigated the synergistic effect of CWQ with oxaliplatin (OXA) on the tumor growth inhibition of orthotopic transplanted colon cancer and explored the underlying mechanism. By generating the orthotopic transplanted nude mouse model of human colon carcinoma, we found that (1) CWQ enhanced OXA-mediated tumor suppression by 4.25-fold. (2) The body weights of nude mice in CWQ group and combination group were increased. (3) The survival time of tumor-bearing nude mice was dramatically improved in CWQ and CWQ/OXA group. (4) CWQ could restore OXA-mediated deregulation of copper transporter genes, hCTR1, ATP7A and ATP7B. (5) OXA-induced drug resistance index for OXA, 5-FU, HCPT and THP were 7.59, 4.28, 5.78 and 4.50 respectively, while the reversal index by combined CWQ treatment were 6.57, 2.61, 4.97 and 3.10, respectively. Our study demonstrates that the repeated intraperitoneal injection of OXA can induce multi-drug resistance of orthotopic transplanted nude mouse model of human colon carcinoma. The CWQ treatment can alleviate OXA-triggered side effects and reverse platinum drug resistance via up-regulation of hCTR1 expression and down-regulation of ATP7A and ATP7B levels.
肠胃清（CWQ）是一种中药配方，长期以来一直用于临床治疗癌症。在本研究中，我们研究了肠胃清与奥沙利铂（OXA）联合对原位移植结肠癌肿瘤生长抑制的协同作用，并探讨了其潜在机制。通过建立人结肠癌原位移植裸鼠模型，我们发现：（1）肠胃清增强奥沙利铂介导的肿瘤抑制作用4.25倍。（2）肠胃清组和联合用药组裸鼠体重增加。（3）肠胃清组和肠胃清/奥沙利铂组荷瘤裸鼠的生存时间显著延长。（4）肠胃清可恢复奥沙利铂介导的铜转运蛋白基因hCTR1、ATP7A和ATP7B的失调。（5）奥沙利铂诱导的对奥沙利铂、5-氟尿嘧啶、羟基喜树碱和吡柔比星的耐药指数分别为7.59、4.28、5.78和4.50，而联合肠胃清治疗后的逆转指数分别为6.57、2.61、4.97和3.10。我们的研究表明，重复腹腔注射奥沙利铂可诱导人结肠癌原位移植裸鼠模型产生多药耐药。肠胃清治疗可减轻奥沙利铂引发的副作用，并通过上调hCTR1表达和下调ATP7A和ATP7B水平逆转铂类药物耐药。
