Abstract
All-trans retinoic acid (ATRA) is an effective agent that induces differentiation, inhibits cell proliferation, and acts as an anticancer agent. ATRA was successfully conjugated with Pluronic F127 via esterification to enhance its anticancer effects. Pluronic-ATRA showed high cytotoxicity and inhibitory concentrations (IC50) 50% lower than those of ATRA in various breast cancer cell lines (4T1:31.16–8.57 μg/mL; EMT6: 50.48–7.08 μg/mL; MDA-MB-231:37.58–8.99 μg/mL; BT474:25.27–9.09 μg/mL). In combination with chemotherapy, Pluronic-ATRA synergistically enhanced the cytotoxic effects of cisplatin (CDDP). Pluronic-ATRA combined with CDDP effectively suppressed breast tumor growth in vivo. The results of this study demonstrate the potential of Pluronic-ATRA as an anticancer agent that can be used in combination therapy against solid tumors.
Highlights
Breast cancer results in the development of destructive tumors and leads to the highest rate of cancer-related deaths in females around the world (Wang et al, 2017; Zhang et al, 2017)
BT474 cells compared to ER- cells, with IC50 values of 9.09 and 25.27 μg/mL, respectively, after treatment with free All-trans retinoic acid (ATRA). These results prove that Pluronic-ATRA monotherapy enhanced inhibitory effects on breast cancer cells compared to those of free ATRA, and that Pluronic F127 itself showed very limited or even no effect on cells
Following the promising results obtained with combined Pluronic-ATRA-CDDP therapy in cancer cells in vitro, we investigated the therapeutic effects of Pluronic-ATRA in solid tumors
Summary
Breast cancer results in the development of destructive tumors and leads to the highest rate of cancer-related deaths in females around the world (Wang et al, 2017; Zhang et al, 2017). Certain studies reported the synergistic therapeutic effects of ATRA and its derivatives in combination with chemotherapeutics such as doxorubicin, CDDP, and paclitaxel in inducing receptormediated cytotoxicity and inhibiting cell growth factors (Liu et al, 2012; Yao et al, 2013; Sun et al, 2015). New hybrid nanoparticles composed of polymeroil-based nano-carriers were used to stabilize RA and increase its stability during delivery (Narvekar et al, 2012) This new delivery system showed more effective anti-cancer activity compared to that of free RA, its preparation is complicated by low solubility, and these nanoparticles cannot be used for co-delivery of RA with other lipophilic drugs. We tested whether lowdose F127-ATRA micelles and the traditional chemotherapeutic agent CDDP showed synergistic cytotoxic effects against breast carcinoma both in vitro and in vivo
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