Inhibitory effect of meloxicam, a cyclooxygenase-2 inhibitor, on N -nitrosobis (2-oxopropyl) amine induced biliary carcinogenesis in Syrian hamsters

Abstract

Pancreaticobiliary maljunction (PBM) is a high risk factor in biliary tract carcinoma. The chemopreventive action of a cyclooxygenase (COX)-2 inhibitor (meloxicam) on N-nitrosobis (2-oxopropyl) amine (BOP)-induced gallbladder cancer in hamster PBM models was investigated. In 7-week-old female Syrian golden hamsters, the extrahepatic bile duct at the distal end of the common duct was ligated and cholecystoduodenostomy was performed (group I). In group II, the same surgery was performed and from week 4 after surgery, 10 mg/kg of BOP was injected subcutaneously once a week with a 1-week interval. In group III, in addition to the measures employed in group II, 5 mg/kg/day of meloxicam was administered once a day, every weekday. Pathological findings in the gallbladder in week 20 after surgery were as follows. In group I, proper epithelium (PE) was predominant and there was no cancer. In group II, PE was predominant, but there was also hyperplasia and atypical epithelium (AE) recognized in 8 of 11 cases (72.7%); the area of AE was more extensive than that in group I. Carcinoma in situ (CIS) was recognized in 4 of 11 cases (36.4%) in group II. Group III showed the same pathological findings as group I. However, compared with group II, the incidence of AE decreased to 27.3% and no cancerous lesion was observed. In week 20 after surgery, the proliferative cell nuclear antigen labeling index in group III was statistically significantly lower than in group II (P = 0.045). No statistically significant differences were noted among the groups in terms of apoptosis labeling index in week 20 after surgery. In conclusion, it was confirmed that meloxicam suppresses carcinogenesis in hamster PBM models and its mechanism may be based on the suppression of cell growth.

Combining kallistatin gene therapy and meloxicam to treat hepatocellular carcinoma in mice

“…(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30) The present study has shown that meloxicam inhibited cell proliferation in situ, supported by our previous report where meloxicam inhibited proliferation of HepG2 cells in vitro. (31) Both studies have shown expression of PCNA, a key cell proliferation marker, was reduced by meloxicam.…”

“…(12,13) Selective COX-2 inhibitors have been regarded as a new group of anticancer drugs based on the observation that expression of COX-2 is elevated in a variety of human cancers (14)(15)(16)(17)(18) including HCC, (19,20) and COX-2 has been shown to promote growth and inhibit apoptosis of cancer cells. (21) A number of studies have investigated the use of meloxicam, a selective COX-2 inhibitor, in inhibiting growth of cancers of ovarian, (22) bladder, (23) biliary duct, (24) breast, (25) lung, (26) and colon. (27) Meloxicam has also shown anticancer activity to treat HCC in vitro and in vivo.…”

Radiosensitizing potential of the selective cyclooygenase-2 (COX-2) inhibitor meloxicam on human glioma cells

“…The COX-2 inhibitor meloxicam was reported to inhibit growth of various tumor cell types both in vitro and in vivo [10,12,22,23,29,30]. Until now, neither the growth inhibitory capacity nor the radiosensitizing potential of meloxicam was tested on human glioma cells.…”

“…arthritis). The anti-tumor effect of selective COX-2 inhibitors, reported both in vitro and in vivo experimental studies [10][11][12], supported the introduction of these compounds in the clinic. However, the mechanism of action of these inhibitors is not well understood.…”

“…Interestingly, selective COX-2 inhibitors also demonstrated to act as a radiosensitizer [5,[15][16][17][18][19][20][21]. The selective COX-2 inhibitor meloxicam has been shown to inhibit cell proliferation of different cancer cell lines and animal tumors [10,12,[22][23][24][25]. However, no data are available yet on glioma cells.…”