chlortetracycline and Pancreatic-Neoplasms

Polo-like kinase 1 (PLK1) is a serine/threonine protein kinase and plays a critical role in mitosis. PLK1 has also been regarded as a valuable target for cancer treatment, and several PLK1 inhibitors are currently undergoing clinical investigations. In this study, our data show that the expression level of PLK1 is upregulated in human pancreatic cancer cells. Molecular modeling studies indicate that DMTC inhibits PLK1 activity through competitive displacement of ATP from its binding pocket. Our data further show that DMTC suppresses the proliferation of pancreatic cancer cells and induces the formation of multinucleated cells, ultimately resulting in apoptosis. In addition, combination index analysis demonstrates that DMTC acts synergistically with the chemotherapeutic drug gemcitabine in inhibiting the proliferation of pancreatic cancer cells. These results thus suggest a potential of using PLK1 inhibitors for the treatment of pancreatic cancer.

Topics: Adenocarcinoma; Apoptosis; Cell Cycle Proteins; Cell Line, Tumor; Cell Proliferation; Chlortetracycline; Deoxycytidine; Drug Synergism; Gemcitabine; Gene Expression Regulation, Neoplastic; Humans; Molecular Targeted Therapy; Pancreatic Neoplasms; Polo-Like Kinase 1; Protein Serine-Threonine Kinases; Proto-Oncogene Proteins

Topics: Adenocarcinoma; Adult; Blood Coagulation Disorders; Blood Coagulation Tests; Chlortetracycline; Cholecystitis; Female; Gallstones; Gastrointestinal Hemorrhage; Humans; Injections, Intravenous; Middle Aged; Pancreatic Neoplasms; Postoperative Complications