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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.

Author information

Choi KH1, Jeon JY2, Lee YE1, Kim SW3, Kim SY4, Yun YJ5, Park KC6.
1
Department of Urology, CHA Bundang Medical Center, CHA University, Seongnam 463-712, Republic of Korea.
2
Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul 120-752, South Korea; Department of Nuclear medicine, Yonsei University College of Medicine, 50-1, Yonsei-ro, Seodaemun-gu, Seoul, 120-752, Republic of Korea.
3
Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul 120-752, South Korea; Severance Biomedical Science Institute, Yonsei University College of Medicine, 50-1, Yonsei-ro, Seodaemun-gu, Seoul, 120-752, Republic of Korea.
4
Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul 120-752, South Korea.
5
Holosmedic Inc, 925Ho, ITECO, Jojeing-daero, Hanam-si, Gyeonggi-do, Republic of Korea, 12930.
6
Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul 120-752, South Korea; Department of Surgery, Yonsei University College of Medicine, 50-1, Yonsei-ro, Seodaemun-gu, Seoul, 120-752, Republic of Korea. Electronic address: ggiru95@yuhs.ac.