Isoginkgetin inhibits lung cancer cell progression through miR-27a-5p/APEX1 axis

Purpose: To determine the influence of isoginkgetin on the progression of pulmonary carcinogenesis. Methods: A549 cells exposed to isoginkgetin were transfected with miR-27a-5p mimetic and suppressor, as well as short hairpin RNA against apurinic/apyrimidinic endo-deoxyribonuclease 1 (sh-APEX1) for 24 h. Then, the proliferative, migration and invasive potential of A549 cells were determined using CCK-8, wound healing and Transwell assays, respectively. The association between miR-27a-5p and APEX1 was determined by dual-luciferase reporter assay. Results: Isoginkgetin significantly suppressed A549 cell proliferative, migration and invasive activities (p < 0.05). Moreover, isoginkgetin significantly increased miR-27a-5p expression. Furthermore, miR-27a-5p suppressor annulled the influence of isoginkgetin on lung cancer progression. More importantly, the inhibitor directly targeted APEX1, and negatively modulated APEX1 expression (p < 0.05). However, APEX1 knockdown annulled the enhancing effect of miR-27a-5p inhibitor on A549 cell viability, migration and invasion (p < 0.05). Conclusion: Isoginkgetin exerts an anti-lung cancer effect via miR-27a-5p/APEX1 axis. Thus, it is a potential therapy for the management of lung cancer; however, clinical studies are required to validate these findings of this study

VEGF-A/Neuropilin 1 Pathway Confers Cancer Stemness via Activating Wnt/β-Catenin Axis in Breast Cancer Cells

Background/Aims: Targeting cancer stem cells (CSCs) is emerging as a promising method for cancer treatment. We previously indicated that knockdown of Neuropilin 1(NRP-1) could inhibit breast cancer cell proliferation. Here, we continue exploring the roles and mechanisms of VEGF-A/NRP-1 axis in breast CSCs formation. Methods: qRT-PCR was used to detect the levels of VEGF-A and NRP-1 in breast cancer sphere cells and wild-type cells. Mammospheres formation, flow cytometry, soft agar colony and tumor formation assays were performed to evaluate the effects of VEGF-A/NRP-1 on breast cancer stemness. Further HUVECs tube formation, cell invasion assays were carried out to detect the effects of VEGF-A/NRP-1 on breast cancer spheres-induced angiogenesis. Finally, Annexin V/PI apoptosis and CCK8 assays were used to detect the effects of VEGF-A/NRP-1 on chemoresistance. Results: Overexpression of VEGF-A or NRP-1 conferred CSCs-related traits in MCF-7 cells, while knockdown of VEGF-A or NRP-1 reduced CSCs-related traits in MDA-MB-231 cells in vitro and in vivo. Notably, VEGF-A acted in a NRP-1 dependent way. Mechanistically, the VEGF-A/NRP-1 axis conferred CSCs phenotype via activating Wnt/β-catenin pathway. Conclusion: our results suggest that VEGF-A/NRP-1 axis could confer CSCs-related traits and chemoresistance