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Development and Maintenance of a Preclinical Patient Derived Tumor Xenograft Model for the Investigation of Novel Anti-Cancer Therapies
Published on: September 30, 2016
Honokiol: a potent chemotherapy candidate for human colorectal carcinoma
Fei Chen1, Tao Wang, Yi-Feng Wu
1Cancer Institute, Second Affiliated Hospital of Zhejiang University, Hangzhou 310009, Zhejiang province, China.
Aim:
To investigate the anticancer activity of honokiol on RKO, a human colorectal carcinoma cell line in vitro and in vivo, and to evaluate its possible use in clinic.
Methods:
In vitro anticancer activity of honokiol was demonstrated by its induction of apoptosis in tumor cells. We analyzed cell proliferation with MTT assay, cell cycle with flow cytosmeter, DNA fragment with electrophoresis on agarose gels. To test the mechanism of honokiol-induced apoptosis, Western blotting was used to investigate the factors involved in this process. The pharmacokinetics study of honokiol was tested by high phase liquid chromatography. In in vivo study, Balb/c nude mice were incubated with RKO cells. Honokiol was injected intraperitoneally every other day into tumor bearing Balb/c nude mice.
Results:
Our results showed that honokiol induced apoptosis of RKO cells in a time- and dose-dependent manner. At 5-10 microg/mL for 48 h, honokiol induced apoptosis through activating Caspase cascades. Pharmacokinetics study demonstrated that, honokiol could be absorbed quickly by intraperitoneal injection, and maintained in plasma for more than 10 h. In nude mice bearing RKO-incubated tumor, honokiol displayed anticancer activity by inhibiting tumor growth and prolonging the lifespan of tumor bearing mice.
Conclusion:
With its few toxicity to normal cells and potent anticancer activity in vitro and in vivo, honokiol might be a potential chemotherapy candidate in treating human colorectal carcinoma.
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