Ailanthus Altissima-derived Ailanthone enhances Gastric Cancer Cell Apoptosis by Inducing the Repression of Base Excision Repair by Downregulating p23 Expression.

Chemotherapy plays an irreplaceable role in the treatment of GC, but currently available chemotherapeutic drugs are not ideal. The application of medicinal plants is an important direction for new drug discovery. Through drug screening of GC organoids, we determined that ailanthone has an anticancer effect on GC cells in vitro and in vivo. We also found that AIL can induce DNA damage and apoptosis in GC cells. Further transcriptome sequencing of PDX tissue indicated that AIL inhibited the expression of XRCC1, which plays an important role in DNA damage repair, and the results were also confirmed by western blotting. In addition, we found that AIL inhibited the expression of P23 and that inhibition of P23 decreased the expression of XRCC1, indicating that AIL can regulate XRCC1 via P23. The results of coimmunoprecipitation showed that AIL can inhibit the binding of P23 and XRCC1 to HSP90. These findings indicate that AIL can induce DNA damage and apoptosis in GC cells. Meanwhile, AIL can decrease XRCC1 activity by downregulating P23 expression to inhibit DNA damage repair. The present study sheds light on the potential application of new drugs isolated from natural medicinal plants for GC therapy.

[Effects of high dose glucose-insulin-potassium infusion on myocardial injury and serum sFas/ sFasL concentration in acute myocardial infarction].

OBJECTIVE: This study was designed to evaluate reperfusion therapy, co-administered with high dose glucose-insulin-potassium (GIK) treatment on serum soluble Fas/APO-1 (sFas) and Fas ligand (sFasL) concentration in Acute Myocardial Infarction (AMI) patients. METHODS: Seventy-four patients with AMI underwent reperfusion therapy were randomized into GIK group (n = 35) receiving high-dose GIK for 24 hours or a vehicle group (n = 39). Thirty-four control subjects (NC) were also enrolled in the present study. Strepavidin-biotin ELISA was used to determine the serum sFas and sFasL concentration at baseline and different time point (24 h, 3 d, 7 d and 14 d) after reperfusion. RESULTS: (1) The serum concentration of sFas and sFas-L ([sFas] and [sFas-L]) of AMI patients were significantly elevated at baseline as compared with NC (P < 0.01). (2) The [sFas] in GIK and non-GIK group decreased 24 h after reperfusion (P < 0.01 vs. baseline) and then increased during 3-7 d period (P < 0.01 vs. 24 h). (3) The GIK group demonstrated reduced [sFas] at 14 d (P < 0.01 vs. 7 d), with no concomitant changes in the non-GIK group. (4) The [sFasL] in the GIK and non-GIK group were no significant difference during 3-14 d period. CONCLUSION Owing to cardioprotective effects reported here and by others, a high-dose GIK infusion co-administered with the timely establishment of perfusion should be strongly considered as a treatment of choice for AMI.