Effect of resveratrol on doxorubicin resistance in breast neoplasm cells by modulating PI3K/Akt signaling pathway

Abstract

In the study, we probed into the effect of Resveratrol (RES) on Doxorubicin (DOX)-resistant breast neoplasm cell line MCF-7/DOX as well as the mechanism of RES underlying the DOX-resistant breast cancer. CCK-8 assay was utilized to assess the survival rates and sensitivity of breast neoplasm cell lines MCF-7 or MDA-MB-231 to DOX and RES. DOX-resistant MCF-7 cell line was successfully cultivated with DOX dose increasing and was named MCF-7/DOX. Afterwards, wound healing and Transwell assays were performed to measure the migration and invasion capabilities of MCF-7/DOX cells, while cell propagation and apoptosis were determined by colony formation assay and flow cytometry analysis. Both western blotting and immunohistochemistry were conducted to examine the expression of proteins involved in PI3K/Akt signaling pathway. Nude mice xenograft model was constructed to further verify the effects of DOX and RES on breast neoplasm in vivo. RES restored DOX sensitivity in MCF-7/DOX cells, inhibiting biological functions of MCF-7/DOX cells and promoting cell apoptosis in vitro and impeding tumor growth in vivo. It was revealed by the mechanistic studies that MCF-7/DOX cells could regain the drug sensibility with RES treatment through inactivating the PI3K/Akt signal transduction pathway. RES could reverse DOX resistance in breast neoplasm cells and inhibited DOX-resistant breast cancer cell propagation and metastasis and facilitated cell apoptosis by modulating PI3K/Akt signaling pathway. © 2018 IUBMB Life, 70(6):491-500, 2018.

The emerging role of microRNAs and long noncoding RNAs in drug resistance of hepatocellular carcinoma

“…Adriamycin could diffuse into the nucleus of HCC cells, interact with DNA and eventually induce apoptosis. There are some known mechanisms for development of adriamycin resistance of HCC [68][69][70][71][72][73][74][75]. Multiple miRNAs have been reported to be involved in adriamycin resistance in HCC ( Table 2).…”

CYP1B1 as a therapeutic target in cardio-oncology

“…CYP1B1 inhibitors have also been shown to enhance the chemotherapeutic effects of DOX in several cancer cell lines including lung cancer [192][193][194], breast cancer [195][196][197][198][199][200][201], liver cancer [201][202][203][204], glioblastoma [205], prostate cancer [206], colorectal cancer [207,208], gastric cancer [209], and leukemia [210,211]. Importantly, several inhibitors have also been shown to overcome DOX resistance in DOX-resistant cancer cell lines [209,210,[212][213][214][215][216][217]. Although all these compounds (Table 3) are known inhibitors of CYP1B1, the role of CYP1B1 in mediating the chemosensitizing effects of these compounds have not been determined in the summarized studies.…”

Bioinspired Composite, pH-Responsive Sodium Deoxycholate Hydrogel and Generation 4.5 Poly(amidoamine) Dendrimer Improves Cancer Treatment Efficacy via Doxorubicin and Resveratrol Co-Delivery

“…Literature also reported that enhancement of cellular uptake of DOX was achieved due to the inhibition of the activity of P-glycoprotein(P-gp) by the RESV. P-gp is an ATP-binding cassette protein found on the cell membrane that pumps many foreign substances including drugs out of cells [ 13 , 58 ].…”