Abstract
Chemoresistance is the most common cause of chemotherapy failure during breast cancer (BCA) treatment. It is generally known that the mechanisms of chemoresistance in tumors involve multiple genes and multiple signaling pathways,; if appropriate drugs are used to regulate the mechanisms at the gene level, it should be possible to effectively reverse chemoresistance in BCA cells. It has been confirmed that chemoresistance in BCA cells could be reversed by ginsenoside Rh2 (G-Rh2). Preliminary studies of our group identified some drug- resistance specific miRNA. Accordingly, we proposed that G-Rh2 could mediate drug-resistance specific miRNA and corresponding target genes through the gene regulatory network; this could cut off the drug-resistance process in tumors and enhance treatment effects. G-Rh2 and breast cancer cells were used in our study. Through pharmaceutical interventions, we could explore how G-Rh2 could inhibit chemotherapy resistance in BCA, and analyze its impact on related miRNA and target genes. Finally, we will reveal the anti-resistance molecular mechanisms of G-Rh2 from a different angle in miRNA-mediated chemoresistance signals among cells.
Highlights
Breast cancer is one of the most common cancer in women, drug-resistance and toxicity are the leading causes that limit the success of aggressive breast cancer therapy (Deng et al, 2013; Liu et al, 2013; Gong et al, 2014; Wang et al, 2014)
ginsenoside Rh2 (G-Rh2) mediating drug-specific miRNA In previous study, we testified that 5 drug-resistance specific miRNA is related to drug-resistance in MCF-7/ Doc and MCF-7/Adr cells (11, 12), Compared to the two cells without intervention, three miRNAs have significant reversal on resistance to change among the five drug-specific miRNAs after G-Rh2 intervention. (Figure 4)
The residual green fluorescent cells of the MCF-7/Doc and MCF-7/ Adr cells with G-Rh2 intervention coped with the drug was significantly reduced more than the two cells without intervention; suggesting that drug resistance can be reversed by G-Rh2 (Figure 5AB)
Summary
Breast cancer is one of the most common cancer in women, drug-resistance and toxicity are the leading causes that limit the success of aggressive breast cancer therapy (Deng et al, 2013; Liu et al, 2013; Gong et al, 2014; Wang et al, 2014). Ginsenoside Rh2 has been used for more than 2, 000 years in oriental countries It is the major pharmacological active component of ginseng that includes a similar basic structure, which consists of a gonane steroid nucleus that holds 17 carbon atoms settled in a four-trans-ring (Zhang et al, 2012) (Figure 1). There are several mechanisms have been shown to be targeted by miRNAs in drug-resistant breast cancer such as DNA repair (Chen et al, 2012; Ratert et al, 2013; Chan et al, 2013; Kutanzi et al, 2011)
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