期刊
CANCERS
卷 11, 期 6, 页码 -出版社
MDPI
DOI: 10.3390/cancers11060781
关键词
oxaliplatin resistance; colorectal cancer; CBD; NOS3; autophagy; mitochondrial dysfunction
类别
资金
- National Research Foundation (NRF) of Korea - Korean government (MSIP) [NRF-2017R1A2B2011684, NRF-2017R1D1A1B03030703]
- Business for Cooperative R&D Between Industry, Academy, and Research Institute - Korea Small and Medium Business Administration [C0566291]
- Korea Technology & Information Promotion Agency for SMEs (TIPA) [C0566291] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Although oxaliplatin is an effective chemotherapeutic drug for colorectal cancer (CRC) treatment, patients often develop resistance to it. Therefore, a new strategy for CRC treatment is needed. The purpose of this study was to determine the effect of cannabidiol (CBD), one of the components of the cannabis plant, in overcoming oxaliplatin resistance in CRC cells. We established oxaliplatin-resistant cell lines, DLD-1 R and colo205 R, in CRC DLD-1 and colo205 cells. Autophagic cell death was induced when oxaliplatin-resistant cells were treated with both oxaliplatin and CBD. Additionally, phosphorylation of nitric oxide synthase 3 (NOS3) was increased in oxaliplatin-resistant cells compared to that in parent cells. Combined treatment with oxaliplatin and CBD reduced phospho-NOS3 levels and nitric oxide (NO) production and resulted in the production of reactive oxygen species (ROS) by reducing the levels of superoxide dismutase 2, an antioxidant present in the mitochondria, causing mitochondrial dysfunction. Taken together, these results suggest that elevated phosphorylation of NOS3 is essential for oxaliplatin resistance. The combination of oxaliplatin and CBD decreased NOS3 phosphorylation, which resulted in autophagy, by inducing the overproduction of ROS through mitochondrial dysfunction, thus overcoming oxaliplatin resistance.
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