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Received Jan 22, 2018; Revised Mar 2, 2018; Accepted Apr 2, 2018
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1. Introduction
Commonly accepted, bladder cancer (BC) pertains to a malignant tumor with top incidence in urological diseases [1]. Overall, bladder tumors are commonly in the presence of noninvasive urothelial carcinoma and muscle-invasive disease [2]. The invasive subtype of BC is closely associated with metastatic spread and poor prognosis of patients [3]. Despite great advances made in the diagnosis and treatment of BC, therapeutic options are limited and prognosis remains unfavorable [4, 5]. Therefore, elucidating the underlying molecular mechanism of development and progression is conductive to and even decisive on BC treatment.
The application of Chinese traditional medicine in tumor treatment has gained much attention in recent years [6–8]. Melittin with twenty-six amino acids is the essential component of honeybee venom [9]. Prior research generally confirms that honeybee venom is accepted as Chinese medicine and applied for treatment of various diseases, exemplified by arthritis, rheumatism, back pain, cancer, and skin disease [10]. Intriguingly, discussions regarding melittin associated with diverse cancers have dominated research in recent years. In our previous work, we retrieved and analyzed articles from 2010 to now in the PubMed database with the search keyword of melittin and cancer. We found that melittin could induce apoptosis and constrain the progression of tumor cells as a result of regulating critical cancer-related signaling pathways. For example, Jo et al. unveiled that melittin could have an anticancer effect as a result of inducing apoptotic cell death in ovarian cancer through enhancement of death receptors and suppression of the JAK2/STAT3 signaling pathway [11]. A similar anticancer effect in prostate cancer cells was evidenced and materialized through activation of the caspase pathway via inactivation of NF-κB [12]. It has also been reported that melittin could suppress PMA-induced tumor cell invasion by inhibiting NF-κB- and AP-1-dependent MMP-9 expression [13], probably through JNK/p38- and NF-κB-dependent mechanisms [14]. Jeong et al. outlined that melittin suppresses TNF-α-induced HASMC migration through the selective inhibition of MMP-9 expression [15]. Shin et al. illustrated that...