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

作者：Hua Sui, Peiwen Duan, Piaoting Guo, Lishuang Hao, Xuan Liu, Jinhua Zhang, Huirong Zhu, Miaomiao Zhao, Hao Wang, Qi Li, Songpo Wang · 发表于：Oncology Reports · 年份：2017 · DOI：10.3892/or.2017.5917 · 被引用次数：18 · 研究领域：Hedgehog Signaling Pathway Studies、Drug Transport and Resistance Mechanisms、Epigenetics and DNA Methylation

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.