Panoply™ Human JAK2 Knockdown Stable Cell Line

Diffuse large B-cell lymphoma (DLBCL) is a highly heterogeneous malignant tumor characterized by diffuse growth. DCZ0858 is a novel small molecule drug with significant antitumor effects against DLBCL. Here, researchers investigated the inhibitory effects of DCZ0858 on DLBCL cell lines. The results showed that DCZ0858 inhibited cell growth in a concentration-dependent and time-dependent manner, while exhibiting no significant toxicity to normal cells. Furthermore, DCZ0858 induced apoptosis through both intrinsic and extrinsic apoptotic pathways. DCZ0858 also induced cell cycle arrest at the G0/G1 phase, thereby controlling cell proliferation. Further molecular mechanism studies revealed that the JAK2/STAT3 pathway is involved in the DCZ0858-mediated antitumor effect, and JAK2 is a key target for DCZ0858 treatment. Knockdown of JAK2 partially attenuated the antitumor effect of DCZ0858 in DLBCL cells, while JAK2 overexpression enhanced the effect of DCZ0858 in DLBCL cells. In addition, DCZ0858 exhibited similar antitumor effects to the JAK2 inhibitor ruxolitinib, and their combination significantly enhanced the anti-cancer signaling. Tumor xenograft models showed that DCZ0858 inhibited tumor growth in vivo with low toxicity to vital organs, consistent with in vitro data. In summary, DCZ0858 is a promising therapeutic agent for DLBCL.

To determine whether the JAK2/STAT3 pathway is involved in the cellular processes affected by DCZ0858 treatment, researchers constructed JAK2-overexpressing and JAK2-knockdown OCI-LY8 and NU-DUL-1 cell lines (Figure 1a, b). Compared to cells treated with DCZ0858 alone, JAK2-knockdown OCI-LY8 cells showed a significantly increased IC50 value after DCZ0858 treatment (Figure 1c). The same trend was observed in DCZ0858-treated NU-DUL-1 cells. Meanwhile, JAK2 overexpression made the cells more sensitive to DCZ0858, exhibiting a lower IC50 concentration (Figure 1c). Flow cytometry results showed that JAK2 knockdown reduced the rate of DCZ0858-induced apoptosis, while more apoptotic cells were found in the group treated with both DCZ0858 and JAK2 overexpression, indicating that JAK2 is involved in DCZ0858-induced apoptosis in DLBCL cells (Figure 1d). Furthermore, JAK2 knockdown partially attenuated the inhibitory effect of DCZ0858 on DLBCL cell colony formation units (Figure 1e).

Figure 1. The JAK2/STAT3 pathway is involved in DCZ0858-mediated anti-tumor effects in the DLBCL cells. (Lu K, et al., 2020)