Zhi Zhen Fang formula reverses Hedgehog pathway mediated multidrug resistance in colorectal cancer

Sui,Hua; Duan,Peiwen; Guo,Piaoting; Hao,Lishuang; Liu,Xuan; Zhang,Jinhua; Zhu,Huirong; Zhao,Miaomiao; Wang,Hao; Li,Qi; Wang,Songpo

doi:10.3892/or.2017.5917

Zhi Zhen Fang formula reverses Hedgehog pathway mediated multidrug resistance in colorectal cancer

Authors:
- Hua Sui
- Peiwen Duan
- Piaoting Guo
- Lishuang Hao
- Xuan Liu
- Jinhua Zhang
- Huirong Zhu
- Miaomiao Zhao
- Hao Wang
- Qi Li
- Songpo Wang
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Affiliations: Department of Traditional Chinese Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200240, P.R. China, Department of General Practice, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, P.R. China, Department of Gynecology, Shanghai TCM-Integrated Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200082, P.R. China, Department of Traditional Chinese Medicine, Changzheng Hospital, Second Military Medical University, Shanghai 200003, P.R. China, Department of Medical Oncology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, P.R. China
Published online on: August 23, 2017 https://doi.org/10.3892/or.2017.5917
Pages: 2087-2095
Copyright: © Sui et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Zhi-Zhen-Fang (ZZR), a Traditional Chinese Medicine (TCM) formula, has been clinically used in China to treat drug-resistant colorectal cancer (CRC) patients as an adjuvant. In this study, the efficacy of ZZR in suppressing multidrug resistance (MDR) on CRC was evaluated in vitro and in vivo. We observed that ZZR enhanced the sensitivity of chemotherapeutic drugs and induced apoptosis in a dose- and time-dependent mannner in CRC MDR cells. Interestingly, signaling of Hedgehog pathway, particularly Gli1, was also inhibited by ZZR. This effect of ZZR in reversing drug resistance and suppressing Gli1 was attenuated by a Hedgehog activator (SAG). Furthermore, ZZR inhibited MDR CRC tumor growth in a xenograft mouse model as well as downregulated Gli1 levels. This study provided the first direct evidence demonstrating ZZR can attenuate MDR by repressing Hedgehog signaling in human CRC.

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