Journal
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
Volume 26, Issue 21, Pages 5426-5438Publisher
WILEY
DOI: 10.1111/jcmm.17565
Keywords
AFP inhibiting fragments; drug delivery; HCC therapy; protein expression; sorafenib
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Funding
- Hainan Province Science and Technology Special Fund [ZDYF2021SHFZ222]
- National Natural Science Foundation of China [82060514, 81960519, 81660463, 81560450, 3156024]
- Hainan Provincial Association for Science and Technology Program of Youth Science Talent and Academic Innovation [QCXM 201922]
- Leadership in Hainan Medical College Natural Science Foundation [JBGS202106]
- Natural Science Foundation of Hainan Province [20168263, 2019CR204, 2019CXTD406, 821RC1065, 822RC700, 820RC634]
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This study presents a new strategy for treating hepatocellular carcinoma (HCC) by inhibiting its malignant behavior with AFP fragments. A specific AFP fragment was found to be highly expressed in human cells and was shown to synergize with the drug sorafenib to inhibit HCC cell growth and migration while promoting apoptosis.
Alpha fetoprotein (AFP) is associated with hepatocellular carcinoma (HCC) by stimulating the proliferation, metastasis and drug resistance. The application of AFP fragments to inhibit the malignant behaviours induced by AFP is a new strategy for the treatment of HCC. In an effort to design, screen and discover drugs, we attempted to express different human AFP fragments (AFP(220-609), AFP(390-609) and AFP(460-609)) in a Bac-to-Bac system. We found that the AFP(390-609) fragment was highly expressed in the system. Then, we assessed the bioactivity of the fragment in the human liver cancer cell line Bel7402, and the results indicated that the AFP fragment synergized with sorafenib to inhibit the hepatoma cell growth and migration and promote the apoptosis. This study provides a method to produce significant AFP fragments to screen AFP inhibitors for use in HCC therapy.
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