Objectives: To explore the mechanism about how HMG-CoA reductase (HMGR) inhibitor inhibit proliferation and bone metastases of lung adenocarcinoma in vitro and in vivo.Methods: The HMGR inhibitor simvastatin, human lung cancer cell line A549 and Balb/c nude mouse were used in this study. The mice were randomly divided into 2 groups: control group (0.9% NaCl solution, i.v.) and simvastatin group (5mg/ kg simvastatin, i.v.). A scratch assay using A549 cell monolayer was also tested. An invasion assay using collagen-coated membrane in trans-wells was applied to evaluate the effect of simvastatin on the metastatic potential of A549 cells in vitro. The expressions of CD44, PUMA, P53, MMP2 and MMP9 were determined by real-time PCR and western blotting; the phosphorylation status of MAPK/ERK signaling parthway was investigated by western blot. .Results: Compared with the control group, the migration of A549 cells in simvastatin-treated group was markedly inhibited (p ≤ 0.01). Untreated A549 cells showed marked invasion, while simvastatin significantly inhibited the invasion of tumor cells (p ≤ 0.001). Incubation of A549 cells with simvastatin significantly reduced the levels of CD44, MMP2 and MMP9 (p <0.01), while significantly increased p53 (p < 0.01). Simvastatin significantly inhibits tumor growth and bone metastasis in lung cancer xenograft mouse model, simvastatin can inhibit the kinase phosphorylation in MAPK/ERK signaling parthway.Conclusions: The HMGR inhibitor simvastatin prevents proliferation and osteolytic bone metastases of lung adenocarcinoma cells in vitro and vivo. Its mechanism may be associated with regulation of CD44, P53, MMP family and inactivation of MAPK/ERK signaling parthway.
Adipose stromal/stem cells (ADSCs) could regulate malignancy behaviors of breast cancer, which was due to adipose-derived cytokines in part, such as leptin and resistin. Recently, peptides have been demonstrated to be potential targets for cancer therapy. It's valuable to analyze the characters of adipose-secreted peptides systematically. In this study, we isolated primary adipocytes from adipose tissue adjacent to breast tumor and breast benign lesions respectively, and then co-cultured breast cancer cells MCF-7 with tumor adjacent adipocytes (TAAs)/breast benign adipocytes (BBAs) separately. Compared to BBAs, TAAs could promote proliferation and migration ability of MCF-7. Then we extracted and purified peptides from supernatant of TAAs and BBAs using ultrafiltration, and the effects of TAAs-derived peptides compound on breast cancer cells appeared accordance with the adipose cells. 100 peptides, which were derived from 90 protein precursors, were found to be differentially secreted between TAAs and BBAs by LC-MS/MS (p < 0.05). Gene Ontology (GO) and Pathway analyses appeared that these altered peptides were mainly contributed to cell adhesion, and regulation of Ras-protein signal transduction. These results showed that these differentially secreted peptides could regulate breast cancer cell malignancy, which indicated that they could be potential therapeutic targets and diagnostic bio-marker for breast cancer. Citation Format: Fu Z, Li W, Wu H, Huang X, Li J, Sun C, Tang J, Yin Y. Adipose-derived peptides from breast cancer patients promote the malignancy of breast cancer MCF-7 cells [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P5-07-15.
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