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Oncotarget ; 6(9): 7280-92, 2015 Mar 30.
Article in English | MEDLINE | ID: mdl-25730901

ABSTRACT

We studied whether bee venom (BV) inhibits cervical tumor growth through enhancement of death receptor (DR) expressions and inactivation of nuclear factor kappa B (NF-κB) in mice. In vivo study showed that BV (1 mg/kg) inhibited tumor growth. Similar inhibitory effects of BV on cancer growth in primary human cervical cancer cells were also found. BV (1-5 µg/ml) also inhibited the growth of cancer cells, Ca Ski and C33Aby the induction of apoptotic cell death in a dose dependent manner. Agreed with cancer cell growth inhibition, expression of death receptors; FAS, DR3 and DR6, and DR downstream pro-apoptotic proteins including caspase-3 and Bax was concomitantly increased, but the NF-κB activity and the expression of Bcl-2 were inhibited by treatment with BV in tumor mice, human cancer cell and human tumor samples as well as cultured cancer cells. In addition, deletion of FAS, DR3 and DR6 by small interfering RNA significantly reversed BV-induced cell growth inhibitory effects as well as NF-κB inactivation. These results suggest that BV inhibits cervical tumor growth through enhancement of FAS, DR3 and DR6 expression via inhibition of NF-κB pathway.


Subject(s)
Bee Venoms/therapeutic use , Uterine Cervical Neoplasms/drug therapy , Animals , Apoptosis , Cell Line, Tumor , Cell Proliferation , Cell Survival , Female , Humans , Mice , Mice, Inbred BALB C , Mice, Nude , NF-kappa B/metabolism , RNA, Small Interfering/metabolism , Receptors, Tumor Necrosis Factor/metabolism , Receptors, Tumor Necrosis Factor, Member 25/metabolism , Transfection , Xenograft Model Antitumor Assays , fas Receptor/metabolism
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