ABSTRACT
c-Myc is a transcription factor involved in the Myc/Max/Mxd signal regulatory network. c-Myc plays important roles in human development and the oncogenesis or progression of different types of tumors. Current studies have shown that c-Myc mutations or expression changes are present in more than 70% of tumors. Therefore, c-Myc-targeted inhibitors might become a new strategy for tumor therapy. Currently, there is no clinical treatment for targeting c-Myc. With the continuous study aiming at the c-Myc targeted clinical application, Omomyc has become a representative c-Myc inhibitor by direct inhibition of c-Myc in tumors, which may be a feasible clinical treatment strategy. Although targeting c-Myc has broad prospects in cancer treatment, direct inhibition of c-Myc still has many risks and challenges. Therefore, in this review, firstly, we will summarize the regulatory network and biological functions of c-Myc in cells. Secondly, the potential significance of targeting c-Myc or its homologues in tumor therapy will be discussed. Additionally, the challenges faced by c-Myc as a potential therapeutic target in clinical application will be summarized. Finally, we will also discuss the advantages and disadvantages of some c-Myc inhibitors that have been discovered to date, such as small molecule inhibitors and protein and peptide inhibitors, therefore providing the theoretical basis for c-Myc targeted clinical therapy in cancer.
ABSTRACT
<p><b>OBJECTIVE</b>This study compared Wistar rat with spontaneously hypertensive rat (SHR) on the electrophysiology and coupling force of the smooth muscle cells in the cerebral arteriolar segments and observe the influence of 18beta-glycyrrhetinic acid(18beta-GA) on the gap junctions between the arterial smooth muscle cells.</p><p><b>METHODS</b>The outer layer's connective tissue of the cerebral arteriolar segments was removed. Whole-cell patch clamp recordings were used to observe the 18beta-GA's impaction on the arteriolar segment membrane's input capacitance (C(input)), input conductance (G(input)) and input resistance (R(input)) of the smooth muscle cells.</p><p><b>RESULTS</b>(1) The C(input) and G(input) of the SHR arteriolar segment smooth muscle cells was much higher than the Wistar rats, there was significant difference (P < 0.05). (2) 18beta-GA concentration-dependently reduced C(input) and G(input) (or increase R(input)) on smooth muscle cells in arteriolar segment. IC50 of 18beta-GA suppression's G(input) of the Wistar rat and SHR were 1.7 and 2.0 micromol/L respectively, there was not significant difference (P > 0.05). After application of 18beta-GA concentration > or = 100 micrmol/L, the C(input), G(input) and R(input) of the single smooth muscle cells was very close.</p><p><b>CONCLUSION</b>Gap junctional coupling is enhanced in the SHR cerebral arterial smooth muscle cells. 18beta-GA concentration-dependent inhibits Wistar rat's and SHR cerebral arteriolar gap junctions between arterial smooth muscle cells. The inhibitory potency is similar between the two different rats. When 18beta-GA concentration is > or = 100 micromol/L, it can completely block gap junctions between arteriolar smooth muscle cells.</p>