The growth and repair of adult skeletal muscle are due in part to activation of muscle precursor cells, commonly known as satellite cells or myoblasts. These cells are responsive to a variety of environmental cues, including mechanical stimuli. The overall goal of the research is to examine the role of mechanical signalling mechanisms in muscle growth and plasticity through utilisation of cell culture systems where other potential signalling pathways (i.e. chemical and electrical stimuli) are controlled. To explore the effects of decreased mechanical loading on muscle differentiation, mammalian myoblasts are cultured in a bioreactor (rotating cell culture system), a model that has been utilised to simulate microgravity. C2C12 murine myoblasts are cultured on microcarrier beads in a bioreactor and followed throughout differentiation as they form a network of multinucleated myotubes. In comparison with three-dimensional control cultures that consist of myoblasts cultured on microcarrier beads in teflon bags, myoblasts cultured in the bioreactor exhibit an attenuation in differentiation. This is demonstrated by reduced immunohistochemical staining for myogenin and alpha-actinin. Western analysis shows a decrease, in bioreactor cultures compared with control cultures, in levels of the contractile proteins myosin (47% decrease, p < 0.01) and tropomyosin (63% decrease, p < 0.01). Hydrodynamic measurements indicate that the decrease in differentiation may be due, at least in part, to fluid stresses acting on the myotubes. In addition, constraints on aggregate size imposed by the action of fluid forces in the bioreactor affect differentiation. These results may have implications for muscle growth and repair during spaceflight.
The potential role of non-steroidal anti-inflammatory drug (NSAID) therapy in the prevention and treatment of cancer has generated considerable research interest. Phosphatidylcholine (PC)-associated NSAIDs decrease the gastrointestinal side effects of NSAID therapy, and may be more effective than traditional NSAIDs in limiting tumor growth. In the present study, human cells representing three major breast cancer subtypes were cultured with aspirin, indomethacin and PC-associated forms of each drug, with PC alone as a control. All tested drugs decreased the tumor cell number after 8 days of culture, with PC-NSAIDs having the greatest inhibitory effect, and NSAIDs alone, particularly aspirin, having the least effect. PC alone was effective in limiting the proliferation of all cell lines, suggesting that the two components of PC-NSAIDs have an additive effect. The ELISA results did not support a strong role for inhibition of cyclooxygenase enzymes in the decrease in cancer cell proliferation, which may account for the limited effectiveness of aspirin alone. PC-NSAIDs, particularly indomethacin-PC, are attractive candidate drugs in the prevention and treatment of different types of breast cancer, including triple negative breast cancer.
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