RESUMO
Imbalance of redox homeostasis may be responsible for the resistance of cancer to chemotherapy. Currently, increasing studies demonstrated that vitamin K3 (VK3), which promoted the production of ROS, had potential to be developed as an anti-tumor agent. We found SKOV3/DDP cells with high levels of p62 were insensitive to VK3 compared with SKOV3 cells. Furthermore, Nrf2 downstream antioxidant genes such as HO-1(heme oxygenase 1) and NQO1 (NAD (P) H: quinone oxidoreductase 1) were upregulated in SKOV3/DDP cells with VK3 treatment, which indicated VK3 activated Nrf2 signaling in SKOV3/DDP cells. Moreover, co-localization of p62 and Keap1 was also observed. Suppression of p62 expression increased the apoptosis induced by VK3, and the expression of Nrf2, HO-1 and NQO1 were all downregulated in SKOV3/DDP cells. Our results suggested that overexpressed p62 may protect cells from oxidative damage caused by VK3 through activating Keap1/Nrf2 signaling in ovarian cancer.
RESUMO
Tumor cells overexpress antiapoptotic proteins of the Bcl-2 (B-cell leukemia/lymphoma-2) family, which can lead to both escape from cell death and resistance to chemotherapeutic drugs. Recent studies suggest that the endoplasmic reticulum (ER) can produce proapoptotic signals, amplifying the apoptotic signaling cascade. The crosstalk between mitochondria and ER plays a decisive role in many cellular events but especially in cell death. Bcl-2 family proteins located in the ER and mitochondria can influence not only the function of the two organelles but also the interaction between them. Therefore, the Bcl-2 family of proteins may also be involved in the mechanism of tumor chemotherapy resistance by influencing crosstalk between the ER and mitochondria. In this review we will briefly discuss evidence to support this concept.