Search

Background: The enhancement of DNA damage repair is one of the important mechanisms of platinum resistance. Protein cell division cycle 7 (CDC7) is a conserved serine/threonine kinase that plays important roles in the initiation of DNA replication and is associated with chemotherapy resistance in ovarian cancer. However, whether the CDC7 inhibitor XL413 has antitumor activity against ovarian cancer and its relationship with chemosensitivity remain poorly elucidated. Methods: We evaluated the antitumor effects of carboplatin combined with XL413 for ovarian cancer in vitro and in vivo. Cell viability inhibition, colony formation and apoptosis were assessed. The molecules related to DNA repair and damage were investigated. The antitumor effects of carboplatin combined with XL413 were also evaluated in SKOV-3 and OVCAR-3 xenografts in subcutaneous and intraperitoneal tumor models. Results: Sequential administration of XL413 after carboplatin (CBP) prevented cellular proliferation and promoted apoptosis in ovarian cancer (OC) cells. Compared with the CBP group, the expression level of RAD51 was significantly decreased and the expression level of γH2AX was significantly increased in the sequential combination treatment group. The equential combination treatment could significantly inhibit tumor growth in the subcutaneous and intraperitoneal tumor models, with the expression of RAD51 and Ki67 significantly decreased and the expression of γH2AX increased. Conclusions: Sequential administration of CDC7 inhibitor XL413 after carboplatin can enhance the chemotherapeutic effect of carboplatin on ovarian cancer cells. The mechanism may be that CDC7 inhibitor XL413 increases the accumulation of chemotherapy-induced DNA damage by inhibiting homologous recombination repair activity.

In this study, we explore the dynamics of entanglement in an ensemble of qutrits with a lambda-type level structure interacting with single-mode bosons. Our investigation focuses on zero-energy states within the subspace of totally symmetric wave functions. Remarkably, we observe a universal two-stage dynamics of entanglement with intriguing revival behavior. The revival of entanglement is a consequence of the self-purification process, where the quantum state relaxes and converges universally to a special dark state within the system.

The spontaneous breaking of time translation symmetry in periodically driven Floquet systems can lead to a discrete time crystal. Here we study the occurrence of such dynamical phase in a driven-dissipative optomechanical system with two membranes in the middle. We find that, under certain conditions, the system can be mapped to an open Dicke model and realizes a superradiant-type phase transition. Furthermore, applying a suitable periodically modulated drive, the system dynamics exhibits a robust subharmonic oscillation persistent in the thermodynamic limit.