Short hairpin RNA-mediated gene silencing of ADAM17 inhibits the growth of breast cancer MCF-7 cells in vitro and in vivo and its mechanism of action

A disintegrin and metalloprotease 17 (ADAM17) is highly expressed in many malignant tumors and is closely related to their development. We showed in a previous study that silencing of ADAM17 by siRNA inhibited the growth of MCF‑7 breast cancer cells in vitro and in vivo. In the present study, we investigated the effects of ADAM17-short hairpin RNA (ADAM17‑shRNA) on MCF‑7 breast cancer cells and explored the potential action pathway. In vitro, transfection of shRNAs was performed using a lentivirus, and the effects of ADAM17‑shRNA on invasion, proliferation and cell cycle distribution of MCF‑7 cells were assessed by Boyden chamber method, real‑time cell analysis and flow cytometry, respectively. In vivo, MCF‑7 cells with different administrations were transplanted subcutaneously into nude mice, and the effect of ADAM17‑shRNA on the growth of transplanted tumors was assessed. In addition, the morphological structures were observed by H&E staining, and the expression of ADAM17 and Ki‑67 was assessed by immunohistochemistry; expression of ADAM17, EGFR, p‑EGFR, AKT, p‑AKT, ERK and p‑ERK proteins was assessed by western blotting, respectively. Our data showed that ADAM17‑shRNA successfully inhibited ADAM17 mRNA expression, invasion and proliferation of MCF‑7 cells resulting in G0/G1 phase arrest, and significantly inhibited the growth of transplanted tumors with larger areas of necrosis, low expression of ADAM17 and Ki-67 and reduced protein expression of ADAM17, EGFR, p‑EGFR, AKT, p‑AKT, ERK, and p‑ERK in the tumor tissues. The present research suggests that ADAM17‑shRNA can inhibit MCF‑7 cell invasion and proliferation in vitro and inhibit MCF‑7 xenograft growth in vivo through the EGFR/PI3K/AKT and EGFR/MEK/ERK signaling pathways.