Proliferation and metastasis are significantly malignant characteristics of human lung cancer, but the underlying molecular mechanisms are poorly understood. Chromobox 4 (CBX4), a member of the Polycomb group (PcG) family of epigenetic regulatory factors, enhances cellular proliferation and promotes cancer cell migration. However, the effect of CBX4 in the progression of lung cancer is not fully understood. We found that CBX4 is highly expressed in lung tumours compared with adjacent normal tissues. Overexpression of CBX4 significantly promotes cell proliferation and migration in human lung cancer cell lines. The knockdown of CBX4 obviously suppresses the cell growth and migration of human lung cancer cells in vitro. Also, the proliferation and metastasis in vivo are blocked by CBX4 knockdown. Furthermore, CBX4 knockdown effectively arrests cell cycle at the G0/G1 phase through suppressing the expression of CDK2 and Cyclin E and decreases the formation of filopodia through suppressing MMP2, MMP9 and CXCR4. Additionally, CBX4 promotes proliferation and metastasis via regulating the expression of BMI-1 which is a significant regulator of proliferation and migration in lung cancer cells. Taken together, these data suggest that CBX4 is not only a novel prognostic marker but also may be a potential therapeutic target in lung cancer.

Diabetic retinopathy (DR) is one of the most prominent microvascular complications of diabetes, which remains the leading cause of legal blindness in the world. Arctiin, a bioactive compound from Arctium lappa L., has been reported to have antidiabetic activity. In this study, we investigated the effect of arctiin on a human retinal capillary endothelial cell (HRCEC) line and how arctiin inhibits cell proliferation in high glucose (HG)-induced HRCECs. Results showed that arctiin decreased HG-induced HRCECs proliferation in a dose-dependent manner by inducing cell cycle arrest at the G0/G1 phase. Tube formation assay and immunofluorescence staining indicated that arctiin abrogated tube formation induced by HG-induced HRCECs in a dose-dependent manner via down-regulation of VEGF expression. Mechanistic study indicated that perturbation of the ROCK1/PTEN/PI3K/Akt signalling pathway plays a vital role in the arctiin-mediated anti-proliferative effect. Furthermore, pre-incubation of HRCECs with Y-27632 attenuated arctiin-induced cell cycle arrest, cell proliferation and tube formation inhibition. Y-27632 also reversed the activation of PTEN, the inactivation/dephosphorylation of PI3K/Akt and down-regulation of VEGF. Taken together, the results demonstrated that arctiin inhibits the proliferation of HG-induced HRCECs through the activation of ROCK1 and PTEN and inactivation of PI3K and Akt, resulting in down-regulation of VEGF, which inhibits endothelial cell proliferation.