RESUMEN
As nonselective cation channels, transient receptor potential melastain 2 (TRPM2) channels are widely distributed in the brain, mainly mediate the inflow of Na+ and Ca2+, leading to cell depolarization and the increasement of intracellular concentration of Ca2+, which are involved in many physiological and pathophysiological processes. Due to increased calcium concentration or oxidative stress, channel gating is induced by either direct or indirect formation of adenosine diphosphate ribose (ADPR) that binds to a NUDT9 homology domain (NUDT9-H) in the channel. There is no specific TRPM2 antagonist so far. Considering some pathological processes are mediated by TRPM2 channels, the study and discovery of specific TRPM2 blockers might contribute to the effective treatment of many related diseases.
RESUMEN
<p><b>OBJECTIVE</b>To investigate the anti-tumor effect of intraportal administration of Adv-p53 in the treatment of the liver metastasis in mice.</p><p><b>METHODS</b>2 x 10(5) of MCA-205 cells were injected into the mouse portal vein to establish a murine liver metastasis model. The spleen was transpositioned subcutaneously to enable the administration of Adv-p53 continually into the portal system. Different doses of Adv-p53 were injected intraportally, while HBSS and Adv-CMV were injected intraportaly in the control group. Tumors in the liver were examined on day 21 after Adv-p53 administration.</p><p><b>RESULTS</b>The liver weight in the Adv-p53 treated mice on day 0 group (1.20 +/- 0.34 g) was significantly less than that in the Adv-CMV group (2.59 +/- 0.48 g, P < 0.05). The number of metastatic nodules in the Adv-p53 treated mice on day 0 group (9.0 +/- 9.9) was significantly less than that in the Adv-CMV group (57.1 +/- 11.3, P < 0.05), indicating that intraportal administration of Adv-p53 inhibited the formation of liver metastasis. This anti-tumor effect was in a dose-dependent manner. After the liver metastasis was formed, Adv-p53 was administered intraportally. The liver weight in the Adv-p53 treated mice on day 5 group (1.22 +/- 0.09 g) was significantly less than that in the Adv-CMV group (3.98 +/- 1.01 g , P < 0.05). The number of metastatic nodules in the Adv-p53 treaed mice on day 5 group (5.5 +/- 3.5) was significantly less than that in the Adv-CMV group (113.2 +/- 5.8, P < 0.05). Repeatedly intraportal administration of Adv-p53 could enhance this anti-tumor effect.</p><p><b>CONCLUSION</b>Local administration of Adv-p53 into the portal system would be a useful strategy for the liver metastasis treatment.</p>