Modest Anti-Cancer Activity of a Bile Acid Acylated Heparin Derivative in a PC14PE6 Induced Orthotopic Lung Cancer Model / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: A novel chemically modified heparin derivative, heparin-deoxycholic acid nano-particles, has lower anticoagulant activity, and was recently reported to have significant anti-tumor effects on squamous head and neck cancer cells. Therefore, the aim of this study was to evaluate the anti-tumor effects of heparin-deoxycholic acid nano-particles in a human lung adenocarcinoma cell line. MATERIALS AND METHODS: An orthotopic lung cancer model in 16 mice was developed using intra-thoracic injections of 0.5x10(6) PC14PE6 cells. Ten days after inoculation, the mice were divided into two groups. PBS and Heparin-DOCA particles were injected once a day every 3 days in the tail vein, for a total of 5 injections. The body weight and survival of each mouse were monitored and the tumor size in the lung was measured by SPECT-CT before and after heparin-DOCA nano-particle treatment. RESULTS: IThe HD particles had no significant cytotoxicity when the PC9 cells were treated in vitro. There was no statistical difference in tumor size, body weight and survival between the HD treated and control groups in vivo. Furthermore, there was no difference in the amount of CD31 between tumor tissues in the two study groups. CONCLUSION: HD synthesized with unfractionated heparin had no apparent inhibitory effects on tumor growth in a PC14PE6 cell induced orthotopic lung cancer mouse model. The HD particles did not significantly inhibit tumor-induced angiogenesis at the tumor sites.

Mouse Orthotopic Lung Cancer Model Induced by PC14PE6 / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: This study was undertaken to investigate in detail the xenograft mouse orthotopic lung cancer model induced by PC14PE6 adenocarcinoma cells. MATERIALS AND METHODS: Three cell doses (0.5x10(6); 1x10(6); 2x10(6)) of PC14PE6 cells were injected into the lungs of male BALB/c nude mice by the intrathoracic injection method. The lung and other organs, including brain, liver, spleen, kidney, muscle, adrenal gland, and lymph node on knee, were removed and stained with H/E to detect the presence of tumor cells. RESULTS: The reliable tumorigenicity time in the PC14PE6 adenocarcinoma cell-inoculated BALB/c nude mouse was 10 days after intrathoracic injection. The average life span of the three groups after inoculation was 14 days in the 2x10(6) cells inoculum group; 25 days in the 1x10(6) cells inoculum group; and 32 days in the 0.5x10(6) cells inoculum group. The PC14PE6 adenocarcinoma cells induced orthotopic lung cancer limited within the thorax. CONCLUSIONS: This orthotopic lung cancer model is an efficient cancer model with easy inoculation methods, rapid and high tumorigenicity, and simple monitoring methods for metastasis.

Effects of gamma-Aminobutyric Acid on Intrinsic Cholinergic Action in Exocrine Secretion of Isolated, Perfused Rat Pancreas

gamma-Aminobutyric acid (GABA) has been reported to enhance exocrine secretion evoked not only by secretagogues but also by intrinsic neuronal excitation in the pancreas. The pancreas contains cholinergic neurons abundantly that exert a stimulatory role in exocrine secretion. This study was undertaken to examine effects of GABA on an action of cholinergic neurons in exocrine secretion of the pancreas. Intrinsic neurons were excited by electrical field stimulation (EFS; 15 V, 2 msec, 8 Hz, 45 min) in the isolated, perfused rat pancreas. Tetrodotoxin or atropine was used to block neuronal or cholinergic action. Acetylcholine was infused to mimic cholinergic excitation. GABA (30microM) and muscimol (10microM), given intra-arterially, did not change spontaneous secretion but enhanced cholecystokinin (CCK; 10 pM) -induced secretions of fluid and amylase. GABA (3, 10, 30microM) further elevated EFS-evoked secretions of fluid and amylase dose-dependently. GABA (10, 30, 100microM) also further increased acetylcholine (5microM) -induced secretions of fluid and amylase in a dose-dependent manner. Bicuculline (10microM) effectively blocked the enhancing effects of GABA (30microM) on the pancreatic secretions evoked by either EFS or CCK. Both atropine (2microM) and tetrodotoxin (1microM) markedly reduced the GABA (10microM) -enhanced EFS- or CCK-induced pancreatic secretions. The results indicate that GABA enhances intrinsic cholinergic neuronal action on exocrine secretion via the GABAA receptors in the rat pancreas.

Effects of gamma-Aminobutyric Acid on Pancreatic Amylase Secretion Evoked by Sodium Oleate in Anesthetized Rats

gamma-Aminobutyric Acid (GABA) is contained in pancreatic islet beta-cells although its physiological role in pancreatic exocrine function is completely unknown at the present time. Recently, we have reported that exogenous GABA enhances secretagogue-evoked exocrine secretion in the isolated, perfused rat pancreas. This study was aimed to investigate an effect of exogenous GABA on pancreatic exocrine secretion in vivo evoked by intestinal stimulation. Rats were anesthetized with urethane (1.4 g/kg) after 24-h fast with free access to water. GABA (10, 30 and 100micromol/kg/h), given intravenously, did not change spontaneous pancreatic amylase secretion but dose-dependently elevated the amylase secretion evoked by intraduodenal sodium oleate (0.05 mmol/h). GABA (30micromol/kg/h) also further increased the amylase secretion stimulated by CCK+(30 pmol/kg/h) plus secretin (20 pmol/kg/h) but failed to modify the amylase secretion induced by secretin alone. GABA (10, 30 and 100micromol/kg/h) also dose-dependently elevated pancreatic amylase secretion evoked by CCK+alone. Bicuculline (100micromol/kg/h), a GABAA-receptor antagonist, markedly reduced the GABA-enhanced pancreatic responses to sodium oleate, CCK+plus secretin or CCK+alone. The results indicate that GABA enhances the sodium oleate-evoked pancreatic amylase secretion via GABAA-receptors in anesthetized rats, which may account for elevating the action of CCK+released by sodium oleate.