Drug resistance largely limits the efficacy and efficiency of chemotherapeutics, which is a first-line treatment for liver cancer, consequently triggering a complete failure in clinical application. There are numerous attempts in exploring potential strategies for avoiding drug resistance, but none of them has effectively addressed this problem. Therefore, novel molecular targets and agents proposed for addressing drug resistance are needed. This study established 5-fluorouracil (5-Fu)-resistant HepG2 cells (HepG2/R) and showed that a FOXM1-targeted peptide, P201, reactivated 5-Fu to attenuate HepG2/R cell viability, proliferation, migration and promote apoptosis. Moreover, both pharmacological studies and RNA genomic sequencing results uncovered that combination of P201 and 5-Fu notably decreased expressions of FOXM1, MDR1 and ABCG2 compared to 5-Fu alone, indicating P201 overcame 5-Fu resistance mainly through inhibiting FOXM1 and ABC transporters. Therefore, P201 could inhibit ABC transporters by targeting FOXM1 in HepG-2/R cells, overcoming 5-Fu resistance and enhancing anti-cancer drug sensitivity. FOXM1 may be a new target for overcoming 5-Fu resistance in HepG2 cell while the combination treatment of P201 and 5-Fu may serve as a potential strategy for treating liver cancer.
Oxidative stress negatively affects the in vitro maturation (IVM) of oocytes. Procyanidin B1 (PB1) is a natural polyphenolic compound that has antioxidant properties. In this study, we investigated the effect of PB1 supplementation during IVM of porcine oocytes. Treatment with 100 μM PB1 significantly increased the MII oocytes rate (p <0.05), the parthenogenetic (PA) blastocyst rate (p <0.01) and the total cell number in the PA blastocyst (p < 0.01) which were cultured in regular in vitro culture (IVC) medium. The PA blastocyst rate of regular MII oocytes activated and cultured in IVC medium supplemented with 100 and 150 μM PB1 significantly increased compared with control (p < 0.01 and p < 0.05). We also evaluated the reactive oxygen species (ROS) levels, mitochondrial membrane potential (Δψm) levels, glutathione (GSH) levels, and apoptotic levels in MII oocytes and cumulus cells following 100 μM PB1 treatment. The results showed that the PB1 supplementation decreased ROS production and apoptotic levels. In addition, PB1 was found to increase Δψm levels and GSH levels. In conclusion, PB1 inhibited apoptosis of oocytes and cumulus cells by reducing oxidative stress. Moreover, PB1 improved the quality of oocytes and promoted PA embryo development. Taken together, our results suggest that PB1 is a promising antioxidant additive for IVM of oocytes. 相似文献