Enhanced anti-tumor activity by the combination of TRAIL/Apo-2L and combretastatin A-4 against human colon cancer cells via induction of apoptosis in vitro and in vivo |
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| Authors: | Chong Zhang Rui Wu Hong Zhu Yong-zhou Hu Hai Jiang Neng-ming Lin Qiao-jun He Bo Yang |
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| Affiliation: | 1. Institute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China;2. Zhejiang University-Ecole Normole Superienre Joint Laboratory of Medicinal Chemistry, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China;3. Department of Urology, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003, China;4. Laboratory of Clinical Pharmacy, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, China |
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| Abstract: | The present study indicated that the combination of TRAIL/Apo-2L and CA-4 exerted synergistic anti-proliferative effect against human colon carcinoma cells including SW-620 and HCT-116 in vitro. Moreover, the increased anti-tumor efficacy of TRAIL/Apo-2L combined with CA-4 was further validated on SW-620 xenograft model in nude mice. These enhanced anti-cancer activities were accompanied by caspase-mediated apoptosis. Furthermore, it was identified that NF-κB as the major determinant of TRAIL/Apo-2L resistance could be blocked in cytoplasm by TRAIL/Apo-2L plus CA-4 treatment. Taken together, these findings build the rationale for further (pre)clinical development of TRAIL/Apo-2L and CA-4 against colorectal cancer. |
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| Keywords: | TRAIL/Apo-2L, the tumor necrosis factor (TNF) α-related apoptosis-inducing ligand CA-4, combretastatin A-4 PI, propidium iodide PBS, phosphate buffer saline CI, combination index FLIP, FLICE-inhibitory protein CA-4P, combretastatin A-4 phosphate NF-κB, nuclear factor kappa B DAPI, 6-diamidino-2-phenylindole MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide TPA, 12-O-tetradecanoylphorbol-13-acetate |
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