mobic and Colonic-Neoplasms

The inhibitors of cyclooxygenase (COX)-2 play an important role in cancer chemoprevention. Certain COX-2 inhibitors exert antiproliferative and pro-apoptotic effects on cancer cells.. In this study, meloxicam, which is an enolic acid-type preferential COX-2 inhibitor, was encapsulated in poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles (NPs) to maintain local high concentration, and its efficacy was determined.. NPs were prepared by using salting-out and emulsion-evaporation steps. Meloxicam-loaded NP formulations were evaluated with respect to the drug loading, particle size, polydispersity index, zeta potential, drug release rate, and residual poly(vinyl alcohol) (PVA) percentage. The effects of PLGA and PVA molecular weight variations on the physicochemical properties of NPs were investigated. Stability of meloxicam in NPs was assessed over 3 months. COX-2 expressing human colon adenocarcinoma cell line HT-29 was used in cellular uptake and viability assays.. NPs had a spherical shape and a negative zeta potential, and their size ranged between 170-231 nm with a lower polydispersity index. NPs prepared with high molecular weight PLGA were shown to be physically stable over three months at 4°C. The increase in molecular weight of the polymer and emulsifier reduced the in vitro release rate of meloxicam from NPs. Meloxicam-loaded NPs showed cytotoxic effects on HT-29 cells markedly at 800 µM. Cancer cells had high uptake of coumarin-6-loaded NPs.. The PLGA NPs developed in this study can be a potentially effective drug delivery system of meloxicam for the treatment of colon cancer.

Topics: Adenocarcinoma; Antineoplastic Agents; Biological Transport; Cell Survival; Chemistry, Pharmaceutical; Colonic Neoplasms; Cyclooxygenase 2 Inhibitors; Drug Carriers; Drug Stability; HT29 Cells; Humans; Kinetics; Lactic Acid; Meloxicam; Molecular Weight; Nanoparticles; Particle Size; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer; Polyvinyl Alcohol; Solubility; Surface Properties; Thiazines; Thiazoles

To evaluate the effects of selective and non-selective cyclooxygenase-2 on the growth and apoptosis of colon cancer cell lines in vitro.. The proliferation of colon cancer cells was determined by MTT assay, and the cell cycle progression was analyzed by flow cytometric assay. Annexin V/PI staining in combination with flow cytometric assay was used to detect apoptosis induced by NSAIDs.. It was found that celecoxib, meloxicam and aspirin could inhibit the growth of HT-29 or SW480 cell and showed a concentration dependent pattern. COX-2 protein was expressed in HT-29 and LS174-T, but not in SW480 cells. In addition, PCNA levels in both HT-29 cell and SW480 cells were reduced by aspirin and celecoxib. Both aspirin (10 mmol/ L) and celecoxib (50 micromol/L) induced apoptosis of HT-29 and SW480 colon cancer cells, the apoptosis rates were 4.8%, 17.7% and 5.1%, 20.4% respectively.. Both COX-2 selective and non-selective inhibitors can potentially inhibit the growth of colon cell lines and such inhibitory effect on COX-2 negative colon cancer cells is also evident.

Topics: Apoptosis; Aspirin; Celecoxib; Cell Line, Tumor; Cell Proliferation; Colonic Neoplasms; Cyclooxygenase 2 Inhibitors; Dose-Response Relationship, Drug; Humans; Meloxicam; Pyrazoles; Sulfonamides; Thiazines; Thiazoles

Meloxicam application in complex of prophylactic treatment of patients with colonic cancer, complicated by an acute obturation ileus, had promoted the lowering of postoperative complications rate, caused by inhibition of the inflammation mediators synthesis and connected with him pathologic reactions of the systemic inflammatory response syndrome (SIRS).

Topics: Acute Disease; Antineoplastic Agents; Colonic Neoplasms; Female; Humans; Ileus; Male; Meloxicam; Neoplasm Staging; Postoperative Complications; Thiazines; Thiazoles

The effects of the cyclooxygenase-2 (COX-2) inhibitor, meloxicam, on tumour growth and cachexia have been determined in 2 established murine adenocarcinomas (MAC). At a dose level of 2.5 and 5.0 mgkg(-1), meloxicam produced pronounced inhibition of the growth of the MAC13 tumour, increasing the tumour volume doubling time from 2 to 5 days. Meloxicam also suppressed growth of the MAC16 tumour, which is generally refractory to standard cytotoxic agents, increasing the tumour volume doubling time from 1.5 to 2.5 days at dose levels of 0.5 and 1.0 mgkg(-1). Cachexia was also effectively attenuated at these dose levels. To investigate whether meloxicam exerted a direct effect on the cachectic process, studies on protein degradation were carried out using C(2)C(12) mouse myoblasts in response to a proteolysis-inducing factor (PIF). PIF produced maximum protein degradation at a concentration of 4.2 nM, and this was effectively attenuated by meloxicam at concentrations greater than 1 microM. This suggests that meloxicam may be capable of directly antagonizing the process of muscle catabolism in cachexia.

Topics: Adenocarcinoma; Animals; Body Weight; Cachexia; Colonic Neoplasms; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Dose-Response Relationship, Drug; Isoenzymes; Male; Meloxicam; Mice; Mice, Inbred Strains; Neoplasm Transplantation; Prostaglandin-Endoperoxide Synthases; Thiazines; Thiazoles; Time Factors