Abstract C7: Mechanistic studying involving the combined effect of Cyclooxygenase-2 inhibitor and Cholecystokinin -2 Receptor antagonist on Pancreatic cancer cell

Abstract

Abstract Introduction: Pancreatic ductal adenocarcinoma is the fourth leading cause of cancer death in United States. Due to poor prognosis and increasing incidences, over 80% of the patient are given palliative chemotherapy with combination drugs. Despite decades of efforts, the survival rate still remains 3-6%. Recent studies have shown an association between the gastrointestinal hormone gastrin, the expression of Cholecystokinin -B/ gastrin receptor and an increased generation of COX-2 in colon-carcinoma cells and progression of gastric cancer, suggesting that gastrin has direct stimulating potencies. However, it remains unknown whether the combination of Cholecystokinin -2 (CCK-2) receptor antagonist plus COX-2 inhibitor exerts synergistic antitumor effects on human gastric cancer. Therefore, for a better treatment and understanding the underlying mechanism that leads to pancreatic adenocarcinoma initiation,we further investigated the combined effect of Cyclooxygenase (COX-2) inhibitor and Cholecystokinin receptor -2 (CCK-2) antagonist on pancreatic cancer cells. Thus it is essential to recognize more effective targets/ receptors for treatment of pancreatic cancer. Materials &Methods: Antiproliferative effects were carried out using Cell Proliferation Kinetics,Morphological analysis and MTT Assay. Apoptotic activity was confirmed by DNA Fragmentation, Western Blot analysis and Cell cycle analysis Result and Discussion: To study the combinatorial effect of COX-2 inhibitor and Cholecystokinin antagonist we successfully purified Etoricoxib using HPLC and further characterized by spectroscopic techniques.The anti-proliferative activity of Etoricoxib was checked on various cell lines and it induced proliferation arrest in Miapaca-2, Panc-I, BXPC-3 and ASPC-1 both in time and concentration dependent manner. combinatorial studies was carried out on Pancreatic cancer cells using cytotoxicity and apoptotic techniques. It is thus, a probable insight in stating that it has lesser side effects and thus have selectivity for cancer cell toxicity. Conclusion: The combined effect of Cyclooxygenase-2 inhibitor and Cholecystokinin-2 Receptor antagonists was calculated.The results has indicated that the combination therapy of COX-2 selective inhibitors may be the potential chemotherapeutic strategy for cancer prevention. In the present study, human pancreatic cancer cell lines, in which the CCK-2 receptor and COX-2 were expressed, was applied to examine whether blockade of the CCK-2 receptor and COX-2 exerts synergistic anti-tumor effects on human pancreatic cancer in vitro.In conclusion, both Etoricoxib and YM-022 had growth inhibitory and apoptosis inductive effects on the pancreatic cancer cells through down regulation of Bcl-2 with simultaneously up-regulation of BAX expression which suggest that COX-2 inhibition is new molecular targets for effective therapy against pancreatic cancer. Citation Format: Manisha Sikka, Madhu Chopra. Mechanistic studying involving the combined effect of Cyclooxygenase-2 inhibitor and Cholecystokinin -2 Receptor antagonist on Pancreatic cancer cell. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr C7.