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.

Highlights

  • Bee venom (BV) therapy is the therapeutic application to the treatment of various diseases

  • We found that bee venom (BV) clearly inhibited growth of primary human cervical cancer cells and tumor growth in xenograft female BALB/c nude mice model accompanied with increased DR3 and DR6 expression and NF-κB inactivation

  • We found that BV inhibited cell growth of www.impactjournals.com/oncotarget human cervical cancer cells; Ca Ski and C33A through induction of apoptotic cell death via increase of DR3 and DR6 expression

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Summary

Introduction

Bee venom (BV) therapy is the therapeutic application to the treatment of various diseases. There is a few available information on the effect of BV on human cervical cancer cells. Previous studies presented that inhibition of cancer cell growth and angiogenesis in culture cervical cancer cells [10, 11]. Our present study focused on xenograft model, clinical data using human sample as well as inhibition of human cancer cell growth. Up-regulation of oncogenes and aberrant activation of related signals could be significant in cervical carcinogensis [13]. Blocking agents these signals might be applicable for treatment of the development of cervical cancer

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