Abstract
Chemoresistance has become a prevalent phenomenon in cancer therapy, which alleviates the effect of chemotherapy and makes it difficult to break the bottleneck of the survival rate of tumor patients. Current approaches for reversing chemoresistance are poorly effective and may cause numerous new problems. Therefore, it is urgent to develop novel and efficient drugs derived from natural non-toxic compounds for the reversal of chemoresistance. Researches in vivo and in vitro suggest that ginsenosides are undoubtedly low-toxic and effective options for the reversal of chemoresistance. The underlying mechanism of reversal of chemoresistance is correlated with inhibition of drug transporters, induction of apoptosis, and modulation of the tumor microenvironment(TME), as well as the modulation of signaling pathways, such as nuclear factor erythroid-2 related factor 2 (NRF2)/AKT, lncRNA cancer susceptibility candidate 2(CASC2)/ protein tyrosine phosphatase gene (PTEN), AKT/ sirtuin1(SIRT1), epidermal growth factor receptor (EGFR)/ phosphatidylinositol 3-kinase (PI3K)/AKT, PI3K/AKT/ mammalian target of rapamycin(mTOR) and nuclear factor-κB (NF-κB). Since the effects and the mechanisms of ginsenosides on chemoresistance reversal have not yet been reviewed, this review summarized comprehensively experimental data in vivo and in vitro to elucidate the functional roles of ginsenosides in chemoresistance reversal and shed light on the future research of ginsenosides.
Highlights
Chemoresistance is regarded as the capability of cancer cells to evade or to cope with the presence of therapeutics, and a vital challenge that researchers manage to reverse
More than 90% of cancer patients died from metastatic cancer in different degrees, which was related to chemoresistance to varying degrees (Wilson et al, 2009)
Rg3 could sensitize hypoxia human NSCLC cells to DDP by inhibiting the nuclear factor-κB (NF-κB) pathway thereby retaining the progress of epithelialmesenchymal transition (EMT) and stemness evidenced as reduced expressions of E-cadherin, N-cadherin, sex determining region Y-box 2 (SOX2), NANOG, octamer-binding transcription factor 4 (OCT4), and CD44
Summary
Chemoresistance is regarded as the capability of cancer cells to evade or to cope with the presence of therapeutics, and a vital challenge that researchers manage to reverse. Three measures including chemical drugs, biological therapy and hyperthermia are taken to reverse chemoresistance These methods are not suitable for clinical promotion because of their single target and function property, serious side effects, expensive cost, and high technical requirements. It is reported that 49% of anti-cancer drugs which are characterized as multiple targets, high effectiveness, and low toxicity and availability, come directly or indirectly from natural products (Newman and Cragg, 2016). Among these natural products as cancer therapy, none has probably enjoyed as much worldwide prestige and attention as ginseng (Qi et al, 2010). We hope this review will lay the foundation for the in-depth investigation of the biochemical mechanisms and pharmacological properties of ginsenosides and benefit the future development and utilization of ginsenosides
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