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Synergistic Activity of Paclitaxel, Sorafenib, and Radiation Therapy in advanced Renal Cell Carcinoma and Breast Cancer

Authors
 Kyung Hwa Choi  ;  Jeong Yong Jeon  ;  Young-Eun Lee  ;  Seung Won Kim  ;  Sang Yong Kim  ;  Yeo Jin Yun  ;  Ki Cheong Park 
Citation
 Translational Oncology, Vol.12(2) : 381-388, 2019 
Journal Title
 Translational Oncology 
Issue Date
2019
Abstract
Advanced cancer has been shown to be associated with a higher percentage of epigenetic changes than with genetic mutations. Preclinical models have shown that the combination of paclitaxel, sorafenib, and radiation therapy (RT) plays a crucial role in renal cell carcinoma (RCC) and breast cancer. This study aimed to investigate the involvement of mitochondrial cytochrome c-dependent apoptosis in the mechanism of action of a combination of paclitaxel, sorafenib, and RT in RCC and breast cancer. RCC and breast cancer cell lines were exposed to paclitaxel and sorafenib alone or combined in the presence of radiation, and cell viability was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The synergistic anticancer effects of the combination therapy on cell cycle and intracellular signaling pathways were estimated using flow cytometry and immunoblot analysis. RCC and breast cancer cell line xenograft models were used to examine the antitumor activity in vivo. Our results suggest that paclitaxel, sorafenib, and RT synergistically decreased the viability of RCC and breast cancer cells and significantly induced their apoptosis, as shown by caspase-3 cleavage. Paclitaxel, sorafenib, and radiation cotreatment reduced antiapoptotic factor levels in these cells and, thereby, significantly reduced the tumor volume of RCC and breast cancer cell xenografts. The current study suggests that paclitaxel, sorafenib, and radiation cotreatment was more effective than cotreatment with paclitaxel or sorafenib and radiation. These findings may offer a new therapeutic approach to RCC and breast cancer.
Files in This Item:
T201902365.pdf Download
DOI
10.1016/j.tranon.2018.11.007
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Seung Won(김승원) ORCID logo https://orcid.org/0000-0002-1692-1192
Park, Ki Cheong(박기청) ORCID logo https://orcid.org/0000-0002-3435-3985
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/170901
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