Combined olaparib and oxaliplatin inhibits tumor proliferation by cell cycle arrest and cell apoptosis in XRCC2-defecient colorectal cancer

Hui Ren, Wenhui Wu, Mingzhe Li, Shaohua Yang, Jingyao Chen, Hong Chen, Liang Li, Changhua Zhang, Yulong He

Abstract

Background: Poly(ADP-ribose) polymerase 1 (PARP1) plays an important role in the process of homologous recombination (HR) repair. The aim of this study was to observe the impact of olaparib (PARP1 inhibitor) on oxaliplatin treatment for XRCC2-defecient colorectal cancer (CRC).
Methods: This study examined the influence of treatments on cells with the help of the γ-H2AX foci formation assay. The CCK-8 assay and clonogenic assay were employed to decide the sensitivity of XRCC2-defecient CRC cells to olaparib and/or oxaliplatin. Finally, we investigated the changes in cell cycle and apoptosis with the aid of flow cytometry and western blotting.
Results: Gamma-H2AX focusing analysis has reached the conclusion that Olaparab is not the only factor inducing double-strand breaks (DSBs), but it can affect oxaliplatin-induced DSBs of XRCC2-defatted CRC cells. Cell proliferation of XRCC2-defecient CRC cell lines was restrained by combination treatment rather than olaparib or oxaliplatin alone. The flow cytometry and western blotting results gave the description cells exposed to connection treatment had more G2/M-phase cells and induced apoptosis than control.
Conclusions: The combination of oxaliplatin and oxaliplatin in the treatment of XRCC2-defecient CRC cells provides a promising method for clinical treatment of XRCC2-defecient CRC.