Journal
ONCOLOGY REPORTS
Volume 38, Issue 4, Pages 2087-2095Publisher
SPANDIDOS PUBL LTD
DOI: 10.3892/or.2017.5917
Keywords
colorectal cancer; multidrug resistance; Hedgehog pathway; ZZR; in vitro; in vivo
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Funding
- project from Shanghai Municipal Commission of Health and Family Planning [ZY3CCCX11009]
- National Natural Science Foundation of China [81373862, 81403360, 81573805]
- Program from Xinjiang Autonomous Region [2013911125]
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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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