| Cancer has become one of the leading causes of human morbidity and mortality.Despite the rapid progress in cancer treatment in the past decade or so,it is still very difficult to eradicate tumor cells.Current treatment for colorectal cancer is mostly based on chemotherapy,but chemotherapy is usually accompanied by severe side effects,so there is a need to find safer and more effective adjuvant treatments.Currently,natural active substances are promising alternatives,and numerous studies have shown that many plant active polyphenols are able to exert anti-cancer effects through different pathways,suggesting the possibility of synergistic anti-cancer effects among them.Procyanidins are a large group of polyphenolic compounds formed by the polymerization of different amounts of catechins and epicatechins,which have anti-inflammatory,antioxidant,antiviral,anticancer and other biological functions.Resveratrol is a non-flavonoid polyphenolic compound widely found in peanuts,grapes,thuja and other plants and is known for its excellent antioxidant,anti-inflammatory and anti-tumor properties.Studies on procyanidins and resveratrol have shown that they can exert anticancer effects through a variety of different pathways.Therefore,the combination of procyanidins and resveratrol for cancer treatment may exert synergistic anticancer effects by initiating multiple mechanisms simultaneously.In this study,we investigated the synergistic anticancer effects of peanut red-coat procyanidins and resveratrol in vitro,aiming to provide new ideas for precise preventive interventions and new insights for effective cancer treatment.The main study was as follows:1.Study on the synergistic anti-cancer effect of PSPC combined with RES in vitroThe toxic effects of PSPC combined with RES on CACO-2 and HCT-8 colorectal cancer cells and HEPG-2 and HUH-7 hepatocellular carcinoma cells were examined in vitro by cytotoxicity assay,and the cells that could be synergistically inhibited by PSPC and RES were screened;the clonogenic ability of cancer cells after synergistic killing by PSPC and RES was investigated by cell clone formation assay.The results showed that::(1)Both PSPC and RES inhibited the proliferation of HCT-8 and CACO-2 colorectal cancer cells and HEPG-2 and HUH-7 liver cancer cells in a concentration-dependent manner,but they exerted synergistic proliferation inhibition only on CACO-2 cells.(2)Both PSPC and RES were able to inhibit the clone formation of CACO-2 cells,and the clone formation ability of CACO-2 cells treated with the combination of PSPC and RES was significantly reduced compared with the group treated alone.2.Study on the mechanism of PSPC combined with RES to synergistically inhibit the growth and proliferation of CACO-2 cellsThe effect of PSPC combined with RES on apoptosis and cell cycle of CACO-2 cells was examined by flow cytometry.The results showed that:(1)Both PSPC and RES promoted apoptosis of CACO-2 cells in a concentrationdependent manner,and the pro-apoptotic effect of combined treatment with PSPC and RES was significantly higher when the sample concentration was greater than 75 μM compared to their separate treatment groups.(2)Both PSPC and RES blocked the cell cycle of CACO-2 cells in GO/G1 phase,and this effect was significantly enhanced when they were combined.3、The mechanism of PSPC combined with RES synergistically promoting apoptosis in CACO-2 cellsThe effects of PSPC combined with RES on PI3K/AKT,MAPK/ERK,and NF-κB signaling pathways in CACO-2 cells were examined by Western Blot assay.The results showed that:(1)PSPC and RES were able to synergistically inhibit the phosphorylation of AKT(Thr308),AKT(Ser473)and ERK proteins,suggesting that they can co-inhibit the activation of PI3K/AKT and MAPK/ERK signaling pathways in CACO-2 cells.(2)PSPC and RES can synergistically promote the phosphorylation of IKBα and NF-κB p65 proteins in CACO-2 cells,which represents the ability of PSPC and RES to synergistically activate the NF-κB signaling pathway in CACO-2 cells. |
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