Prokaryotically and eukaryotically expressed interleukin-24 induces breast cancer growth suppression via activation of apoptosis and inhibition of tumor angiogenesis

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Publisher： Spandidos Publications

E-ISSN： 1791-3004|11|5|3673-3681

ISSN： 1791-2997

Source： Molecular Medicine Reports, Vol.11, Iss.5, 2015-01, pp. : 3673-3681

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Abstract

Melanoma differentiationassociated7 (mda7)/interleukin24 (IL24), a unique cytokinetumor suppressor, exerts tumorselective killing activity in numerous types of cancer cell. Although eukaryotically and prokaryotically expressed recombinant human (rh)IL24 proteins have been previously shown to produce potent antitumor effects, to the best of our knowledge, no sidebyside study has been conducted that compares the two proteins directly. In the present study, rhIL24 protein was expressed in BL21 Escherichia coli transformed with the pET21a(+)hIL24 plasmid by isopropylβD1thiogalactopyranoside induction. Following a denaturing and renaturing process, the soluble rhIL24 was purified using a QSepharose column. rhIL24 protein was also expressed in Chinese hamster ovary mammalian cells stably transfected with the pcDNA3hIL24 plasmid. The in vitro antitumor efficacies of the two treatments were compared using the MDAMB231 human breast cancer cell line. Furthermore, the therapeutic efficacies of the bacteriaderived rhIL24 protein and the liposomecoated pcDNA3hIL24 naked plasmid were evaluated in athymic nude mice with subcutaneously xenografted MDAMB231 cell tumors. The prokaryotically expressed/purified rhIL24 protein and the eukaryotically expressed rhIL24 in the cell supernate were revealed to be capable of efficiently suppressing MDAMB231 tumor growth in vitro. Similarly, the administration of bacteriaderived rhIL24 protein and pcDNA3hIL24 naked plasmid also provided therapeutic benefits in the treatment of in vivo MDAMB231 xenografted tumors. The retarded in vitro and in vivo breast cancer growth elicited by rhIL24 was closely associated with the upregulation of the ratio of antiapoptotic B cell lymphoma 2 (Bcl2) to proapoptotic Bcl2associated X protein (Bax), as well as the activation of caspase3 followed by marked induction of apoptosis, and the notable inhibition of tumor angiogenesis. Thus, the results of the present study indicate that prokaryotically expressed rhIL24 protein may be an alternate and promising antitumor agent in human breast cancer or other types of cancer.