Cordycepin down-regulates multiple drug resistant (MDR)/HIF-1α through regulating AMPK/mTORC1 signaling in GBC-SD gallbladder cancer cells.

Gallbladder cancer is the most common malignancy of the bile duct, with low 5-year survival rate and poor prognosis. Novel effective treatments are urgently needed for the therapy of this disease. Here, we showed that cordycepin, the bioactive compound in genus Cordyceps, induced growth inhibition and apoptosis in cultured gallbladder cancer cells (Mz-ChA-1, QBC939 and GBC-SD lines). We found that cordycepin inhibited mTOR complex 1 (mTORC1) activation and down-regulated multiple drug resistant (MDR)/hypoxia-inducible factor 1α (HIF-1α) expression through activating of AMP-activated protein kinase (AMPK) signaling in gallbladder cancer GBC-SD cells. Contrarily, AMPKα1-shRNA depletion dramatically inhibited cordycepin-induced molecular changes as well as GBC-SD cell apoptosis. Further, our results showed that co-treatment with a low concentration cordycepin could remarkably enhance the chemosensitivity of GBC-SD cells to gemcitabine and 5-fluorouracil (5-FU), and the mechanism may be attributed to AMPK activation and MDR degradation. In summary, cordycepin induces growth inhibition and apoptosis in gallbladder cancer cells via activating AMPK signaling. Cordycepin could be a promising new drug or chemo-adjuvant for gallbladder cancer.

[Binding pancreatic duct to mucosa anastomosis].

OBJECTIVE: To study the feasibility of binding pancreatic duct to mucosa anastomosis (BDM)-a complementary procedure to both binding pancreaticojejunostomy and binding pancreaticogastrostomy. METHODS: (1) Animal experimental study:gastrostomy and jejunostomy were performed on six adult New Zealand rabbits. The gastrostomy and jejunostomy shared a same stent (rubber urethral catheter, silicone tube or plastic infusion tube). Both ends of the stent were placed in gastric and enteric cavity. Purse-string suture was performed around the stent before the jejunum and the stomach were brought together for fixation by few stitches. And to observe whether the purse-string suture around a plastic tube, rubber tube or silicon tube inserted into jejunum and/or stomach can prevent leaking out of the jejunal or gastric content to cause peritonitis. (2) Clinically 7 patients were performed with BDM anastomosis. The procedure was consisted of five steps: preparation of the pancreatic stump;preparation of the jejunum; preparation of the fixing sutures between the pancreatic stump and the jejunum; implementation of the anastomosis; lastly, fixation of the jejunum beside the pancreas stump. Post-operative periodic examination of the blood amylase and the amylase in the abdominal drainage. Pancreatic fistula was classified in to two categories: parenchymal fistula (pancreatic cut surface fistula) and anastomotic leakage. RESULTS: Animal experiment did not show any leakage around the plastic tube or silicon tube inserted into jejunum and(or) stomach. There was no anastomotic leak in all the patients. There was transient increase of amylase in two cases, but the volume of drainage did not exceed 50 ml/d and the recovery of the patients was not affected. CONCLUSIONS: BDM is a simple, safe and easy procedure to perform. It provides to the surgeons with a new option in different situations to achieve the most ideal surgical result.