Apelin-13 is extensively expressed in various tissues, particularly breast tissue. Apelin‑13 has been shown to promote tumor proliferation in various types of cancer, including hepatocellular, lung and ovarian cancer. However, the effect and molecular mechanism of apelin‑13 in breast cancer cells remains unclear. The present study investigated the effect of apelin‑13 on MCF‑7. Therefore, cell proliferation was determined by MTT and flow cytometry analysis. The results revealed that apelin‑13 markedly increased cell proliferation. Transwell assays demonstrated that apelin‑13 increased MCF‑7 cell invasion. Apelin‑13 also markedly increased the expression of cyclin D1, extracellular matrix metalloproteinase‑1 and amplified in breast cancer 1 (AIB1) in a dose‑dependent manner by polymerase chain reaction assays. To study the molecular mechanism, cell proliferation, invasion and cyclin D1 were inhibited by pre‑treatment with 10 µM of PD98059 (ERK(1/2) inhibitor). Western blotting results suggested that apelin‑13 significantly enhances the expression of p‑ERK(1/2) in a concentration‑dependent manner. In conclusion, the results suggest that apelin‑13 promoted MCF-7 cell proliferation and invasion via the ERK1/2/AIB1 signaling pathway.

Abstract. Skeletal muscle atrophy is often caused by catabolic conditions including fasting, disuse, aging and chronic diseases, such as chronic obstructive pulmonary disease. Atrophy occurs when the protein degradation rate exceeds the rate of protein synthesis. Therefore, maintaining a balance between the synthesis and degradation of protein in muscle cells is a major way to prevent skeletal muscle atrophy. Ginsenoside Rg1 (Rg1) is a primary active ingredient in Panax ginseng, which is considered to be one of the most valuable herbs in traditional Chinese medicine. In the current study, Rg1 was observed to inhibit the expression of MuRF-1 and atrogin-1 in C2C12 muscle cells in a starvation model. Rg1 also activated the phosphorylation of mammalian target of rapamycin (mTOR), protein kinase B (AKT), and forkhead transcription factor O, subtypes 1 and 3a. This phosphorylation was inhibited by LY294002, a phosphatidylinositol 3-kinase inhibitor. These data suggest that Rg1 may participate in the regulation of the balance between protein synthesis and degradation, and that the function of Rg1 is associated with the AKT/mTOR/FoxO signaling pathway. IntroductionMuscle atrophy is characterized by an increase in protein degradation and reduction in protein synthesis. It is associated with a number of human diseases and catabolic conditions, including fasting, disuse, aging, cancer, neuromuscular diseases, stroke, chronic obstructive pulmonary disease, chronic heart failure, HIV-acquired immunodeficiency syndrome and sepsis (1-5). Muscle volume shrinking and muscle weakness induced by muscular dystrophy typically disrupt and adversely affect the life of patients (3,6-8). Therefore, it is essential to understand the mechanism by which skeletal muscle atrophy is regulated.A large amount of protein hydrolysis has previously been identified to occur during muscle atrophy and the ubiquitin-proteasome system (UPS) has been demonstrated to be involved in this process (9)(10)(11)(12)(13)(14). In this system, the proteins are first conjugated into multiple molecules of ubiquitin. The 26S proteasome then recognizes and degrades the ubiquitinated proteins (15,16). Multiple enzymes regulate the protein ubiquitination; these include E1, the ubiquitin-activating enzyme, E2, the ubiquitin conjugating enzyme and E3 ubiquitin ligases (17,18). E3 ubiquitin ligases serve a major role in the specificity of protein degradation, because the specific binding between the protein substrate and E3 occurs prior to the reaction with ubiquitin (18,19).It has been demonstrated that the insulin-signaling pathway is involved in the inhibition of UPS (20). In this pathway, the phosphorylation of insulin receptor substrate is stimulated when insulin binds its receptor. Phosphatidylinositol 3-kinase (PI3K), an intracellular intermediate, is recruited to phosphorylate a serine/threonine kinase, protein kinase B (AKT) during this process. AKT then phosphorylates the forkhead box class O transcription factors, subtype 1 and 3a (FoxO1 and FoxO3a), which pre...

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