A new herbal formula BP10A exerted an antitumor effect and enhanced anticancer effect of irinotecan and oxaliplatin in the colon cancer PDTX model
- Authors
- Kim, Jinhee; Kim, Hye-Youn; Hong, Suntaek; Shin, Sarah; Kim, Young Ah; Kim, No Soo; Bang, Ok-Sun
- Issue Date
- Aug-2019
- Publisher
- ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
- Keywords
- BP10A; Colon cancer; Combination treatment; Patient-derived tumor xenograft; Synergistic effect
- Citation
- BIOMEDICINE & PHARMACOTHERAPY, v.116
- Journal Title
- BIOMEDICINE & PHARMACOTHERAPY
- Volume
- 116
- URI
- https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/1121
- DOI
- 10.1016/j.biopha.2019.108987
- ISSN
- 0753-3322
- Abstract
- BP10A is a novel two-herb medicine formula, consisting of Descurainiae sophia Semen and Peucedani praer-uptorum Radix. This study was done to evaluate the antitumor efficacy of BP10A and its effect on the efficacy of the anticancer drugs oxaliplatin and irinotecan (CPT-11) in a colon tumor xenograft model. Chemical constituents from the ethanol extracts of BP10A were characterized with the ultra-performance liquid chromatography (UPLC) and each constituent was quantified with the UPLC-diode array detector method. Our study showed that BP10A exerted the cytotoxic effects in two colorectal cancer cell lines and its combination treatments with oxaliplatin or CPT-11 remarkably increased the in vitro cytotoxicity of each cancer drug assessed by the Ez-cytox assay. The in vivo antitumor activity of BP10A was evaluated in three colon cancer patient-derived tumor xenograft (PDTX) models with different genetic backgrounds. Oral administration with BP10A (250 and 500 mg/kg, daily) delayed tumor growth by 34-70% in the all PDTX models. Similarly, intraperitoneal injection of oxaliplatin (6 mg/kg) or CPT-11 (20 mg/kg) also suppressed tumor growth by 31.8-60.5% or by 24.3-50.4%, respectively. Furthermore, the combination treatment of BP10A with oxaliplatin or CPT-11 remarkably enhanced the antitumor activity of each anti-cancer drug and delayed tumor growth by 47.1-74.6% or by 74.4-82.9%, respectively. In accordance with the antitumor activity, the Ki-67 expression for tumor cell proliferation and the CD31 for angiogenesis were decreased, and TUNEL staining for tumor cell apoptosis was remarkably increased by the co-treatment of BP10A and the anticancer drugs as well as by each treatment of BP10A, oxaliplatin or CPT-11. Conclusively, BP10A has a strong tumor inhibitory effect against colon cancer and a synergistic effect with anticancer drugs, suggesting that BP10A could be considered as a good therapeutic candidate for the treatment of colon cancer.
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